Background: Up to 30% of Psoriasis (PsO) patients are prone to develop Psoriatic Arthritis (PsA). Agreement on how to identify PsO patients at risk of developing PsA is still lacking (1). Objectives: To identify predictors of PsA development in PsO patients through a systematic literature review (SLR) and meta-analyses (MA). Methods: MEDLINE, EMBASE and COCHRANE databases were searched (up to February 22nd, 2020). The PICO framework (population = PsO patients; intervention = clinical, environmental, imaging and genetic features; comparator = not applicable; outcome = PsA development) was used to design searches and define the eligibility of studies for inclusion. The MA focuses on 3 major features as possible predictors: i) PsO skin and nail involvement; ii) musculoskeletal (MSK) complaints; iii) inflammation and structural damage detected by imaging (Table 1). The sample estimates of the relative risk were pooled only when the studies were homogeneous in terms of cohort of patients, follow-up, study design and metrics. Results: 4698 articles were screened for eligibility, 110 underwent a full reading and 29 were finally included. Figure 1 shows the study flow-chart for article selection. Though pooling was judge not appropriate, 5/7 prospective studies significantly support a predictive value of PsA development in patients with severe PsO (n=174635). While the predictive value of nail involvement is not well defined (n=2202), the pooled estimate from two cohort studies (n=474) supports nail pitting as predictor of PsA (RR=2.14 [1.32; 3.46]). Moving to the MSK complaints, the risk of developing PsA is about two times greater in PsO with than without arthralgia (pooled RR: 2.15 [1.16, 3.99]) within 2 years. Lastly, PsO patients with inflammation or structural damage detected by imaging are nearly four times more likely to develop PsA within 1-2 years (pooled RR from 4 cohort studies (n=247): 3.72 [2.12; 6.51]) (Table 1). The incidence rate of PsA varies from 1.34 to 5.9/100 p-ys in PsO and from 10.9 to 12.5/100 p-ys in PsOAr. Table 1. Studies reporting the major features as possible predictors of PsA development. PsO skin – severity PsO nail involvement PsO nail lesions Variables Relative Risk [95%CI] Follow-up Wilson, 2009 PsO nail involvement HR adjusted : 2.24 [1.26; 3.98] 13.1±8.8 ys Faustini, 2015 PASI score + PsO nail involvement /σ= -0.18[-0.84; 0.48] RR: 0.95 [0.37; 2.47] 1.2±0.2 ys Eder, 2016 PASI score PsO nail involvement Type of PsO nail lesions HR (>20vs<10): 5.39 [1.64; 17.7] HR unadjusted : 1.36 [0.76; 2.45] HR unadjusted : 2.21 [1.24; 3.92] 4.1±2.1 ys Eder, 2017 PASI score + Type of PsO nail lesions HR unadjusted : 1.05 [1.01; 1.09] HR unadjusted : 1.98 [0.83; 4.74] 3.8±2.1 ys Lewinson, 2017 PsO severity defined from medications HR adjusted (moderate/severe vs mild): 5.02 [4.18; 6.04] 5.1 ys Egeberg, 2018 PsO severity defined from medications RR (severe vs mild): 1.31 [1.18; 1.46] 18 ys Elnady, 2019 PASI score + PsO nail Involvement /σ= 0.79[-0.37; 1.95] RR: 1.43 [0.38; 5.31] 2 ys Green, 2020 PsO severity defined from medication RR (severe vs mild): 2.79 [2.49; 3.13] 5.8 ys MSK-complaints Variables Incident-PsA cases Follow-up Faustini, 2015 Arthralgia RR: 1.98 [0.75; 5.19] 1.2±0.2 ys Eder, 2017 Arthralgia HR adjusted : 2.59 [1.15; 5.88] 3.8±2.1 ys Zabotti, 2019 Arthralgia RR: 4.44 [0.54; 36.72] 1.6±0.5 ys Simon D, 2020 Arthralgia RR: 2.04 [0.86; 4.86] 2.4±1.5 ys Sub-clinical inflammation or structural damage detected by imaging Variables Incident-PsA cases Follow-up Faustini, 2015 MRI RR: 2.10 [0.75; 5.90] 1.2±0.2 ys Elnady, 2019 MSK-US RR: 5.38 [1.17; 24.63] 2 ys Zabotti, 2019 MSK-US RR: 6.86 [0.83; 56.63] 1.6±0.5 ys Simon D, 2020 HR-pQCT RR: 4.32 [1.96; 9.55] 2.3±1.4 ys Conclusion: Arthralgia and inflammation and/or structural damage detected by imaging are predictive features, likely prodromal, of PsA development. PsO severity and nail pitting are clinical manifestations related to PsA development. Figure 1. References: [1]Zabotti A, et al. Curr Rheumatol Rep. 2020 May 16;22(6):24. doi: 10.1007/s11926-020-00891-x. Disclosure of Interests: Alen Zabotti Speakers bureau: UCB, Novartis, Janssen, Paid instructor for: Amgen, Consultant of: Janssen, Orazio De Lucia Speakers bureau: Not relevant for this type of study, Consultant of: Not relevant for this type of study, Grant/research support from: Not relevant for this type of study, Garifallia Sakellariou Consultant of: AbbVie, Novartis, Alberto Batticciotto Speakers bureau: Not relevant for this type of study, Consultant of: Not relevant for this type of study, Grant/research support from: Not relevant for this type of study, Gilberto Cincinelli: None declared, Ivan Giovannini: None declared, Luca Idolazzi Speakers bureau: Eli Lilly, UCB, Celgene, MSD, Abbvie, Novartis, Paid instructor for: UCB, Gabriella Maioli Speakers bureau: Not relevant for this type of study, Consultant of: Not relevant for this type of study, Grant/research support from: Not relevant for this type of study, Ilaria Tinazzi Speakers bureau: Not relevant for this type of study, Consultant of: Not relevant for this type of study, Grant/research support from: Not relevant for this type of study, Daniel Aletaha Speakers bureau: not relevant for this type of study, Consultant of: not relevant for this type of study, Grant/research support from: not relevant for this type of study, Salvatore De Vita Consultant of: GSK, Roche, Grant/research support from: Not relevant for this type of study, Antonio Marchesoni Speakers bureau: not relevant for this type of study, Consultant of: not relevant for this type of study, Grant/research support from: not relevant for this type of study, Josef S. Smolen Speakers bureau: Not relevant for this type of study, Consultant of: Not relevant for this type of study, Grant/research support from: Not relevant for this type of study, Annamaria Iagnocco Speakers bureau: not relevant for this type of study, Paid instructor for: not relevant for this type of study, Consultant of: not relevant for this type of study, Grant/research support from: not relevant for this type of study, Dennis McGonagle Speakers bureau: ABBVIE, CELGENE, PFIZER, MSD, NOVARTIS, JANSSEN, UCB, GILEAD, BMS, LILLY, Grant/research support from: ABBVIE, CELGENE, PFIZER, MSD, NOVARTIS, JANSSEN, UCB, GILEAD, BMS, LILLY, Roberto Caporali Speakers bureau: Abbvie, Amgen, BMS, Celltrion, Galapagos, Gilead, Lilly, Pfizer, Roche, UCB, Sanofi, Fresenius Kabi, Samsung bioepis, MSD, Consultant of: Galapagos, Gilead, Lilly, Janssen, MSD
Non-specific musculoskeletal pain is common in subjects destined to develop psoriatic arthritis (PsA). We evaluated psoriatic patients with arthralgia (PsOAr) compared with psoriasis alone (PsO) and healthy controls (HCs) using ultrasonography (US) to investigate the anatomical basis for joint symptoms in PsOAr and the link between these imaging findings and subsequent PsA transition.A cross-sectional prevalence analysis of clinical and US abnormalities (including inflammatory and structural lesions) in PsOAr (n=61), PsO (n=57) and HCs (n=57) was performed, with subsequent prospective follow-up for PsA development.Tenosynovitis was the only significant sonographic feature that differed between PsOAr and PsO (29.5% vs 5.3%, p<0.001), although synovitis and enthesitis were numerically more frequent in PsOAr. Five patients in PsOAr and one in PsO group developed PsA, with an incidence rate of 109.2/1000 person-years in PsOAr vs 13.4/1000 person-years in PsO (p=0.03). Visual Analogue Scale pain, Health Assessment Questionnaire, joint tenderness and US active enthesitis were baseline variables associated with PsA development.Tenosynovitis was associated with arthralgia in subjects with psoriasis. Baseline US evidence of enthesitis was associated with clinical PsA development in the longitudinal analysis. These findings are relevant for enriching for subjects at risk of imminent PsA development.
Treatment of psoriatic arthritis (PsA) may pose some difficulties in clinical practice, with a relevant proportion of patients being refractory to at least two courses of biological treatment, 1 thus leading to persistent inflammation/pain and diminished quality of life (sometimes regardless of objective signs of inflammation). 1 Hence, there is a need to find alternative treatments in such a subset of biologics-refractory PsA patients.In this analysis, we investigated the efficacy of bimekizumab (BKZ), an inhibitor of IL17A and IL17F, in biologicsrefractory PsA (defined as the failure of at least two courses of biological treatment) in a real-life setting.Specifically, we considered psoriatic subjects from our combined dermatology-rheumatology clinic who also had active PsA and were candidates for BKZ therapy for skin disease.A comprehensive rheumatological examination including swollen joint count (SJC) in 66 joints, tender joint count (TJC) in 68 joints and Leeds Enthesitis Index (LEI), collection of PsA related Patient Reported Outcomes (PROs) and a sonographic assessment in 48 joints, 36 tendons and 12 enthesis were performed at baseline (w0), as well as week 12 (w12) and 24 (w24).The active sonographic site count score (ie, US active site count) was defined by a radiologist, blinded to the clinical evaluation as the sum of active synovitis, 2 active tenosynovitis 3 and active enthesitis 4 in each patient.All data are expressed as mean values or percentages; statistical analysis was performed by using Mann-Whitney U-test with a p-value of 0.05 deemed as statistically significant.In total, seven psoriatic patients (mean age 54.5 ± 15 years; 4/7 male; Psoriasis Area Severity Index (PASI): mean 8.5 ± 5.1) with active and biologics-refractory PsA (mean Disease Activity Index for Psoriatic Arthritis (DAPSA): 35.9 ± 20) were included in this analysis (Table 1).Among them, 5/7 (71.4%) were classified as difficult to treat (D2T) PsA patients (defined as failure of at least two mechanisms of action + persistent moderate disease activity). 5At w12, 5/7 patients (71.4%) experienced a significant joint improvement with achievement of DAPSA-low disease activity, whereas PASI100 was achieved in 5/7 patients (71.4%).Six out of seven patients (85.7%) reached the Minimum Clinically Important Difference (MCID) for both DAPSA and PASI. 6,7Interestingly, we observed an improvement even in three out of four patients who had previously failed other IL-17A inhibitors.In terms of mean values, we observed DAPSA and PASI amelioration, with figures of 13.8 ± 6.9 (Δ DAPSA 22.1) and 3.2 ± 7.4 (Δ PASI 5.3), respectively; at week 24, DAPSA-low disease activity and PASI100 rates were maintained (Figure 1).Notably, six out seven patients (85.7%) did not display significant joint inflammatory objective findings during baseline clinical and sonographic examinations (SJC mean 0.67 ± 0.81; US active site count mean 0.83 ± 0.75; CRP mean 0.21 ± 0.1 mg/dl) despite experiencing active disease according to TJC (mean 11.3 ± 15.8) and patient-reported outcomes (mean PtGA 6.33 ± 2.7; mean VAS pain 6.2 ± 2.5).Considering such a subset of patients, BKZ showed a 40% decrease in TJC (Δ 4.5; p=0.26) and a significant reduction of Patient Global Assessment (PtGA) and Visual Analogue Scale (VAS) pain scores (p=0.025 and p=0.025,
Objective: Salivary gland ultrasound (SGUS) is emerging as a valid tool in the management of primary Sjögren's syndrome (pSS). This study aimed to investigate whether pSS patients with normal-appearing or pathological SGUS findings showed different clinical, laboratory, and pathologic pSS-related features, and to compare the results by using two different SGUS scores. Methods: Consecutive pSS patients, according to the ACR-EULAR classification criteria, were evaluated. Salivary glands were scored using the early 1992 score by De Vita et al. and the latest 2019 OMERACT score, both being semiquantitative 0–3 scoring systems focused on ultrasonographic parenchymal inhomogeneity (grades 0 and 1, normal-appearing; grades 2 and 3, pathological). The patients were then divided into two groups: “SGUS normal-appearing” if all the salivary glands had normal-appearing parenchyma (grade 0 or 1), or “SGUS pathological” if the grade was 2 or 3 in at least one salivary gland. The associations between SGUS and pSS-related clinical, laboratory, and pathological features were then investigated in the two groups. Results: One hundred pSS patients were evaluated, the mean age (±SD) was 60.9 ± 12.0 years, and mean disease duration was 11.7 ± 7.2 years. Twenty-nine out of 100 (29%) patients were in the “SGUS normal-appearing” group and 71/100 (71%) were in the “SGUS pathological” group. A normal-appearing SGUS was significantly associated with the absence of anti-La/SSB antibodies ( p < 0.001) and normal unstimulated salivary flow rate ( p = 0.02) by both univariate and multivariate analyses. By univariate analysis, a normal-appearing SGUS was significantly associated also with the absence of rheumatoid factor ( p = 0.002) and of serum monoclonal component ( p = 0.003), ESSDAI < 5 ( p = 0.03), and with a negative lip biopsy ( p = 0.029). No associations were found with other items, including anti-Ro/SSA ( p = 0.145), Schirmer's test ( p = 0.793), ESSPRI ( p = 0.47), and demographic data. No differences in these results were observed by using the two SGUS scoring systems. Conclusion: The SGUS allowed the identification of different phenotypes of pSS, and different SGUS scores focused on salivary gland inhomogeneity may be effective to this end.
Abstract A major goal in juvenile idiopathic arthritis (JIA) long-term management is to ensure a successful transition to adult age. This study aims to assess transition outcomes in a group of JIA patients during their passage from pediatric to adult healthcare assistance at a single center. This is a cross-sectional study. All patients with JIA undergoing a transition from the Pediatric Rheumatology Service of the IRCCS “Burlo Garofolo” Hospital, Trieste, to the adult Rheumatology Service of “Santa Maria della Misericordia” Hospital, Udine, between 2017 and 2022, were enrolled. Clinical and laboratory data were collected. A semi-structured survey exploring patients’ satisfaction was distributed through email. Numerical variables were compared using Student’s t -test or Mann–Whitney test. Categorical variables were compared with Fisher’s exact test. We recruited 36 patients (26 female, 72.2%): 9 with polyarticular course JIA, 13 oligoarticular, 8 psoriatic arthritis, 3 systemic JIA, and 3 enthesitis-related arthritis. The mean age at transition was 18.6 ( Q 1– Q 3, 18.3–19.1). JADAS-27 score significantly decreased after the transition, with a mean difference of 2.6 ( p = 0.014). No patients were lost to follow-up, and in 8 out of 36 (22.2%), a step-up therapy was needed within the first 12 months. Among these, no correlation was found with the JIA subtype, age at onset, type of involved joints, and other variables explored. Finally, the 15 patients who answered the survey (response rate 50%) were satisfied about the transition process. This study described a real-life transition experience from pediatric to adult rheumatology care, showing good transition outcome measures, with no patients lost to follow-up and a reduction of JADAS-27 score after completing the process.
Salivary gland ultrasound (SGUS) is the imaging modality of choice for the assessment of parotid and submandibular gland parenchyma. Being highly effective, non-invasive and easy to perform, SGUS has become increasingly popular among specialists in assessing salivary gland (SG) abnormalities, including those commonly found in primary Sjögren's syndrome (pSS). SGUS may be useful in the assessment of pSS and its complications, the most serious being the development of non-Hodgkin's lymphoma (NHL). SGUS may also be useful in the characterization and differential diagnosis of diffuse and focal abnormalities commonly associated with pSS, and may act as a guide for core-needle biopsy (CNB), an established, safe, and feasible technique, which provides enough viable tissue for the diagnosis and assessment of lymphoproliferative diseases of the SG. The combination of SGUS with other tools, such as sonoelastography and artificial intelligence (AI), could further improve the usefulness of SGUS in the management of pSS. In this perspective, we summarize current and future applications of SGUS in pSS.
Psoriasis (PsO) and Psoriatic Arthritis (PsA) are chronic, immune-mediated diseases that share common etiopathogenetic pathways. Up to 30% of PsO patient may later develop PsA. In nearly 75% of cases, skin psoriatic lesions precede arthritic symptoms, typically 10 years prior to the onset of joint symptoms, while PsO diagnosis occurring after the onset of arthritis is described only in 15% of cases. Therefore, skin involvement offers to the rheumatologist a unique opportunity to study PsA in a very early phase, having a cohort of psoriatic "risk patients" that may develop the disease and may benefit from preventive treatment. Progression from PsO to PsA is often characterized by non-specific musculoskeletal symptoms, subclinical synovio-entheseal inflammation, and occasionally asymptomatic digital swelling such as painless toe dactylitis, that frequently go unnoticed, leading to diagnostic delay. The early diagnosis of PsA is crucial for initiating a treatment prior the development of significant and permanent joint damage. With the ongoing development of pharmacological treatments, early interception of PsA has become a priority, but many obstacles have been reported in daily routine. The introduction of digital technology in rheumatology may fill the gap in the physician-patient relationship, allowing more targeted monitoring of PsO patients. Digital technology includes telemedicine, virtual visits, electronic health record, wearable technology, mobile health, artificial intelligence, and machine learning. Overall, this digital revolution could lead to earlier PsA diagnosis, improved follow-up and disease control as well as maximizing the referral capacity of rheumatic centers.
