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1.
J Vis Exp ; (205)2024 Mar 01.
Article En | MEDLINE | ID: mdl-38497631

Psoriasis plaque severity metrics, such as induration (thickness), erythema (redness), and desquamation (scaliness), are associated with the subsequent development of psoriatic arthritis (PsA) among cutaneous-only psoriasis patients (patients with skin or nail psoriasis but no psoriatic arthritis). These metrics can be used for PsA screening. However, a key challenge in PsA screening is to optimize accessibility and minimize costs for patients, while also reducing the burden on healthcare systems. Therefore, an ideal screening tool consists of questions that patients can answer without a physician's assistance. Although reference images can be used to help a patient self-assess erythema and desquamation severity, a patient would need a tactile induration reference card to self-assess induration severity. This protocol describes how to create an induration reference card, the Psoriasis Thickness Reference Card, as well as how to use it to assess lesion induration severity. Administration of reference images for erythema and desquamation and a Psoriasis Thickness Reference Card for induration to 27 psoriasis patients showed that patients were moderately successful at self-assessing the severity of these three metrics. These findings support the feasibility of a future PsA screening test that patients can complete without the need for physician assistance.


Arthritis, Psoriatic , Nail Diseases , Psoriasis , Humans , Arthritis, Psoriatic/diagnosis , Arthritis, Psoriatic/pathology , Psoriasis/diagnosis , Skin/pathology , Nail Diseases/pathology , Erythema
3.
J Autoimmun ; 143: 103167, 2024 02.
Article En | MEDLINE | ID: mdl-38301504

IL-23-activation of IL-17 producing T cells is involved in many rheumatic diseases. Herein, we investigate the role of IL-23 in the activation of myeloid cell subsets that contribute to skin inflammation in mice and man. IL-23 gene transfer in WT, IL-23RGFP reporter mice and subsequent analysis with spectral cytometry show that IL-23 regulates early innate immune events by inducing the expansion of a myeloid MDL1+CD11b+Ly6G+ population that dictates epidermal hyperplasia, acanthosis, and parakeratosis; hallmark pathologic features of psoriasis. Genetic ablation of MDL-1, a major PU.1 transcriptional target during myeloid differentiation exclusively expressed in myeloid cells, completely prevents IL-23-pathology. Moreover, we show that IL-23-induced myeloid subsets are also capable of producing IL-17A and IL-23R+MDL1+ cells are present in the involved skin of psoriasis patients and gene expression correlations between IL-23 and MDL-1 have been validated in multiple patient cohorts. Collectively, our data demonstrate a novel role of IL-23 in MDL-1-myelopoiesis that is responsible for skin inflammation and related pathologies. Our data open a new avenue of investigations regarding the role of IL-23 in the activation of myeloid immunoreceptors and their role in autoimmunity.


Arthritis, Psoriatic , Dermatitis , Psoriasis , Humans , Arthritis, Psoriatic/pathology , Interleukin-17/genetics , Interleukin-17/metabolism , Neutrophils/metabolism , Skin/pathology , Dermatitis/pathology , Inflammation , Interleukin-23/genetics , Interleukin-23/metabolism , Receptors, Cell Surface/metabolism , Lectins, C-Type/genetics
4.
Scand J Rheumatol ; 53(3): 188-198, 2024 May.
Article En | MEDLINE | ID: mdl-38275170

OBJECTIVE: To investigate the effects of methotrexate (MTX) and the tumour necrosis factor inhibitor infliximab (IFX) on immune cells derived from peripheral blood mononuclear cells (PBMCs) and synovial fluid mononuclear cells (SFMCs) of inflammatory arthritis patients. METHOD: Phytohaemagglutinin (PHA)-induced proliferation of healthy donors' PBMCs and synovial intermediate monocytes (CD14+CD16+ cells) in SFMCs derived from psoriatic arthritis (PsA) and rheumatoid arthritis (RA) patients was determined by flow cytometry following co-culture with IFX and MTX. PHA-induced interferon-γ (IFN-γ) production in PBMCs was measured by enzyme-linked immunosorbent assay. The drugs' effect on mRNA expression in SFMCs was determined by quantitative polymerase chain reaction. RESULTS: The combination of IFX 10 µg/mL + MTX 0.1 µg/mL had the strongest inhibitory effect on PBMC proliferation (91%), followed by MTX 0.1 µg/mL (86%) and IFX 10 µg/mL (49%). In PHA-stimulated PBMCs, IFN-γ production was reduced by IFX 10 µg/mL, MTX 0.1 µg/mL, and IFX 10 µg/mL + MTX 0.1 µg/mL by 68%, 90%, and 85%, respectively. In SFMCs, IFX 10 µg/mL significantly reduced CD14+CD16+ cells compared to medium (PsA 54%, p < 0.01; RA 46%, p < 0.05), while MTX had no effect on this population. IFX + MTX led to a similar suppression of CD14+CD16+ cells as achieved by IFX alone. The drugs had different impacts on SFMC gene expression. CONCLUSION: Both IFX and MTX effectively inhibited PBMC proliferation and IFN-γ production, but only IFX reduced synovial monocytes and pro-inflammatory gene expression in SFMCs, suggesting a differential impact of IFX and MTX on critical inflammatory cell populations ex vivo.


Arthritis, Psoriatic , Arthritis, Rheumatoid , Humans , Methotrexate/pharmacology , Methotrexate/therapeutic use , Infliximab/pharmacology , Infliximab/therapeutic use , Leukocytes, Mononuclear/metabolism , Synovial Fluid , Arthritis, Psoriatic/drug therapy , Arthritis, Psoriatic/pathology , Anti-Inflammatory Agents/therapeutic use
5.
Biomed J ; 47(1): 100655, 2024 Feb.
Article En | MEDLINE | ID: mdl-37598797

Nod-like receptors (NLRs) are innate immune receptors that play a key role in sensing components from pathogens and from damaged cells or organelles. NLRs form signaling complexes that can lead to activation of transcription factors or effector caspases - by means of inflammasome activation -Inflammatory arthritis (IA) culminating in promoting inflammation. An increasing body of research supports the role of NLRs in driving pathogenesis of IA, a collection of diseases that include rheumatoid arthritis (RA), psoriatic arthritis (PsA), ankylosing spondylitis, and pediatric arthritis. In this review, we briefly discuss the main drivers of IA diseases and dive into the evidence for - and against - various NLRs in driving these diseases. We also review the studies examining the use of NLR and inflammasome inhibitors as potential therapies for IA.


Arthritis, Psoriatic , Arthritis, Rheumatoid , Spondylitis, Ankylosing , Humans , Child , Arthritis, Psoriatic/pathology , Arthritis, Psoriatic/therapy , Inflammasomes , NLR Proteins
6.
Rheumatology (Oxford) ; 63(1): 218-225, 2024 Jan 04.
Article En | MEDLINE | ID: mdl-37137278

OBJECTIVES: Approximately 20% of people with psoriasis develop PsA. Although genetic, clinical and environmental risk factors have been identified, it is not known why some people with psoriasis develop PsA. The skin disease is traditionally considered the same in both. This study compares transcriptional changes in psoriasis and PsA skin for the first time. METHODS: Skin biopsies were collected from healthy controls (HC), and uninvolved and lesional skin from patients with PsA. Bulk tissue sequencing was performed and analysed using the pipeline Searchlight 2.0. Transcriptional changes in PsA skin were compared with existing sequencing data from participants with psoriasis without PsA (GSE121212). Psoriasis and PsA datasets could not be directly compared as different analysis methods were used. Data from participants with PsA in the GSE121212 dataset were used for validation. RESULTS: Skin samples from 9 participants with PsA and 9 HC were sequenced, analysed and compared with available transcriptomic data for 16 participants with psoriasis compared with 16 HC. Uninvolved skin in psoriasis shared transcriptional changes with lesional skin in psoriasis, but uninvolved skin in PsA did not. Most transcriptional changes in psoriasis and PsA lesional skin were shared, but immunoglobulin genes were upregulated in PsA lesional skin specifically. The transcription factor POU2F1, which regulates immunoglobulin gene expression, was enriched in PsA lesional skin. This was confirmed in the validation cohort. CONCLUSIONS: Immunoglobulin genes are upregulated in PsA but not in psoriasis skin lesions. This may have implications for the spread from the cutaneous compartment to other tissues.


Arthritis, Psoriatic , Psoriasis , Humans , Arthritis, Psoriatic/pathology , Genes, Immunoglobulin , Psoriasis/metabolism , Skin/pathology , Gene Expression Regulation
7.
NMR Biomed ; 37(1): e5040, 2024 Jan.
Article En | MEDLINE | ID: mdl-37740595

The purpose of this study is to investigate the use of ultrashort echo time (UTE) magnetic resonance imaging (MRI) techniques (T1 and magnetization transfer [MT] modeling) for imaging of the Achilles tendons and entheses in patients with psoriatic arthritis (PsA) compared with asymptomatic volunteers. The heels of twenty-six PsA patients (age 59 ± 15 years, 41% female) and twenty-seven asymptomatic volunteers (age 33 ± 11 years, 47% female) were scanned in the sagittal plane with UTE-T1 and UTE-MT modeling sequences on a 3-T clinical scanner. UTE-T1 and macromolecular proton fraction (MMF; the main outcome of MT modeling) were calculated in the tensile portions of the Achilles tendon and at the enthesis (close to the calcaneus bone). Mann-Whitney-U tests were used to examine statistically significant differences between the two cohorts. UTE-T1 in the entheses was significantly higher for the PsA group compared with the asymptomatic group (967 ± 145 vs. 872 ± 133 ms, p < 0.01). UTE-T1 in the tendons was also significantly higher for the PsA group (950 ± 145 vs. 850 ± 138 ms, p < 0.01). MMF in the entheses was significantly lower in the PsA group compared with the asymptomatic group (15% ± 3% vs. 18% ± 3%, p < 0.01). MMF in the tendons was also significantly lower in the PsA group compared with the asymptomatic group (17% ± 4% vs. 20% ± 5%, p < 0.01). Percentage differences in MMF between the asymptomatic and PsA groups (-16.6% and -15.0% for the enthesis and tendon, respectively) were higher than the T1 differences (10.8% and 11.7% for the enthesis and tendon, respectively). The results suggest higher T1 and lower MMF in the Achilles tendons and entheses in PsA patients compared with the asymptomatic group. This study highlights the potential of UTE-T1 and UTE-MT modeling for quantitative evaluation of entheses and tendons in PsA patients.


Achilles Tendon , Arthritis, Psoriatic , Humans , Female , Adult , Middle Aged , Aged , Young Adult , Male , Achilles Tendon/diagnostic imaging , Arthritis, Psoriatic/diagnostic imaging , Arthritis, Psoriatic/pathology , Magnetic Resonance Imaging/methods , Protons
8.
Front Immunol ; 14: 1274060, 2023.
Article En | MEDLINE | ID: mdl-38124740

Objectives: The abnormal DNA damage response is associated with upregulation of the type-1 interferon (IFN-I) pathway in certain rheumatic diseases. We investigated whether such aberrant mechanisms operate in psoriatic arthritis (PsA). Methods: DNA damage levels were measured by alkaline comet assay in peripheral blood mononuclear cells from 52 PsA patients and age-sex-matched healthy individuals. RNA expression of IFIT1, MX1 and IFI44, which are selectively induced by IFN-I, was quantitated by real-time polymerase chain reaction and their composite normalized expression resulted in IFN-I score calculation. RNA expression of IL1ß, IL6, TNF, IL17A and IL23A was also assessed in PsA and control subgroups. Results: In PsA, DNA damage accumulation was increased by almost two-fold compared to healthy individuals (olive tail moment arbitrary units, mean ± SD; 9.42 ± 2.71 vs 4.88 ± 1.98, p<0.0001). DNA damage levels significantly correlated with serum C-Reactive-protein and IL6 RNA expression in PBMCs. Despite increased DNA damage, the IFN-I score was strikingly lower in PsA patients compared to controls (-0.49 ± 6.99 vs 4.24 ± 4.26; p<0.0001). No correlation was found between IFN-I pathway downregulation and DNA damage. However, the IFN-I score in a PsA subgroup was lower in those patients with higher IL1ß expression, as well as in those with higher TNF/IL23A PBMCs expression. Conclusion: DNA damage in PsA correlates with measures of inflammation but is not associated with the IFN-I pathway induction. The unexpected IFN-I downregulation, albeit reminiscent to findings in experimental models of spondyloarthritis, may be implicated in PsA pathogenesis and explained by operation of other cytokines.


Arthritis, Psoriatic , Interferon Type I , Humans , Arthritis, Psoriatic/pathology , Interferon Type I/metabolism , Leukocytes, Mononuclear/metabolism , Interleukin-6/metabolism , DNA Damage , RNA/metabolism
9.
BMJ Open ; 13(9): e078539, 2023 09 28.
Article En | MEDLINE | ID: mdl-37770264

INTRODUCTION: Psoriatic arthritis (PsA) affects around 150 000 people in the UK of whom around 50% require treatment with biologics. The most used biologics for PsA target tumour necrosis factor (TNF) or interleukin-17A (IL-17A). About 50% of patients respond to each, but it is not currently possible to predict response for individual patients, necessitating sequential treatment steps. A recent proof of concept study in PsA suggested that using peripheral immunophenotype to choose therapy could improve time to treatment response.This study will test the hypothesis, within an open-label parallel-group biomarker-stratified multicentre randomised controlled trial, which the baseline proportion of CD4+T cells with an activated type 17 immunophenotype (Th17 levels) predicts response to IL-17A or TNF inhibitors in PsA. Additional analyses will identify if the model can be refined by combining additional clinical and immunophenotypic factors. Statistical modelling will be used to predict the likely effectiveness of these approaches compared with standard care. METHODS AND ANALYSIS: Patients with PsA eligible to start their first biologic as part of standard care are recruited and baseline blood tests are taken for immunophenotyping. Participants are stratified equally by Th17 levels and randomised 1:1 to receive either TNF (adalimumab) or IL-17A (secukinumab) inhibitors. The primary analysis will establish the interaction between baseline immunophenotype and treatment on the primary outcome (achievement of minimal disease activity criteria at week 24). In secondary analysis, modelling will identify if this prediction model can be optimised further by incorporating clinical phenotypes and additional immunophenotyping techniques. ETHICS AND DISSEMINATION: Ethical approval for the study was granted by the North West Preston Research Ethics Committee (ref 21/NW/0016). Dissemination will be via conference presentations and peer-reviewed publications, aiming to impact on treatment guidelines. TRIAL REGISTRATION NUMBER: ISRCTN17228602.


Antirheumatic Agents , Arthritis, Psoriatic , Biological Products , Humans , Arthritis, Psoriatic/drug therapy , Arthritis, Psoriatic/pathology , Antirheumatic Agents/therapeutic use , Interleukin-17/therapeutic use , Precision Medicine , Biological Products/therapeutic use , Treatment Outcome , Randomized Controlled Trials as Topic , Multicenter Studies as Topic
10.
Expert Opin Investig Drugs ; 32(8): 741-753, 2023.
Article En | MEDLINE | ID: mdl-37655430

INTRODUCTION: Psoriatic Arthritis (PsA) is an inflammatory arthritis that is present in approximately 25% of psoriasis patients. Currently, several targeted therapies are available to manage PsA; however, many patients fail these therapies. Several new therapeutic options, with differing mechanisms of action, are currently being evaluated. AREAS COVERED: This article reviews available results from phase I to phase III trials of several investigational monoclonal antibodies that the FDA has not yet approved for PsA. The proposed mechanisms of the new therapeutic agents and their relevance to the pathogenesis of PsA will be discussed. The investigational agents' efficacy and safety will be summarized, and their potential clinical applications for managing PsA will be contemplated. EXPERT OPINION: Due to recent advances in understanding psoriatic arthritis, therapeutic agents are increasingly focused on inhibiting interleukin-17 and interleukin-23 pathways. Various strategies have been used to inhibit these cytokines, demonstrating favorable efficacy and acceptable safety profile.


Arthritis, Psoriatic , Biosimilar Pharmaceuticals , Psoriasis , Humans , Arthritis, Psoriatic/drug therapy , Arthritis, Psoriatic/pathology , Antibodies, Monoclonal/adverse effects , Biosimilar Pharmaceuticals/adverse effects , Psoriasis/drug therapy , Interleukin-23
11.
Int Immunopharmacol ; 121: 110453, 2023 Aug.
Article En | MEDLINE | ID: mdl-37331300

Extracellular matrix (ECM) is a three-dimensional network entity composed of extracellular macromolecules. ECM in synovium not only supports the structural integrity of synovium, but also plays a crucial role in regulating homeostasis and damage repair response in synovium. Obvious disorders in the composition, behavior and function of synovial ECM will lead to the occurrence and development of arthritis diseases such as rheumatoid arthritis (RA), osteoarthritis (OA) and psoriatic arthritis (PsA). Based on the importance of synovial ECM, targeted regulation of the composition and structure of ECM is considered to be an effective measure for the treatment of arthritis disease. This paper reviews the current research status of synovial ECM biology, discusses the role and mechanism of synovial ECM in physiological status and arthritis disease, and summarizes the current strategies for targeting synovial ECM to provide information for the pathogenesis, diagnosis and treatment of arthritis disease.


Arthritis, Psoriatic , Arthritis, Rheumatoid , Gout , Humans , Arthritis, Psoriatic/pathology , Synovial Membrane/pathology , Arthritis, Rheumatoid/pathology , Gout/pathology , Extracellular Matrix , Homeostasis
12.
Int J Mol Sci ; 24(12)2023 Jun 15.
Article En | MEDLINE | ID: mdl-37373313

Arthritis has a high prevalence globally and includes over 100 types, the most common of which are rheumatoid arthritis (RA), osteoarthritis (OA), psoriatic arthritis (PsA), and inflammatory arthritis [...].


Arthritis, Psoriatic , Arthritis, Rheumatoid , Osteoarthritis , Humans , Arthritis, Psoriatic/drug therapy , Arthritis, Psoriatic/pathology , Synovial Fluid , Arthritis, Rheumatoid/drug therapy , Arthritis, Rheumatoid/pathology , Osteoarthritis/therapy , Osteoarthritis/pathology
13.
Sci Rep ; 13(1): 5329, 2023 04 01.
Article En | MEDLINE | ID: mdl-37005487

Nail psoriasis occurs in about every second psoriasis patient. Both, finger and toe nails can be affected and also severely destroyed. Furthermore, nail psoriasis is associated with a more severe course of the disease and the development of psoriatic arthritis. User independent quantification of nail psoriasis, however, is challenging due to the heterogeneous involvement of matrix and nail bed. For this purpose, the nail psoriasis severity index (NAPSI) has been developed. Experts grade pathological changes of each nail of the patient leading to a maximum score of 80 for all nails of the hands. Application in clinical practice, however, is not feasible due to the time-intensive manual grading process especially if more nails are involved. In this work we aimed to automatically quantify the modified NAPSI (mNAPSI) of patients using neuronal networks retrospectively. First, we performed photographs of the hands of patients with psoriasis, psoriatic arthritis, and rheumatoid arthritis. In a second step, we collected and annotated the mNAPSI scores of 1154 nail photos. Followingly, we extracted each nail automatically using an automatic key-point-detection system. The agreement among the three readers with a Cronbach's alpha of 94% was very high. With the nail images individually available, we trained a transformer-based neural network (BEiT) to predict the mNAPSI score. The network reached a good performance with an area-under-receiver-operator-curve of 88% and an area-under precision-recall-curve (PR-AUC) of 63%. We could compare the results with the human annotations and achieved a very high positive Pearson correlation of 90% by aggregating the predictions of the network on the test set to the patient-level. Lastly, we provided open access to the whole system enabling the use of the mNAPSI in clinical practice.


Arthritis, Psoriatic , Deep Learning , Nail Diseases , Psoriasis , Humans , Arthritis, Psoriatic/pathology , Retrospective Studies , Severity of Illness Index , Psoriasis/pathology , Nail Diseases/pathology , Nails/pathology
14.
Egypt J Immunol ; 30(2): 73-82, 2023 Apr.
Article En | MEDLINE | ID: mdl-37031409

Immune mediated inflammatory diseases (IMIDs) are a diverse range of diseases that affect joints with early overlapping symptoms. Rheumatoid arthritis (RA) and psoriatic arthritis (PsA) are the most common disorders sharing immune-pathogenic mechanisms that cause peripheral arthritis. Psoriasis (Ps) is a chronic inflammatory autoimmune skin disease characterized by epidermal hyperplasia with significant invasion by inflammatory cells. New biomarkers are required to enable an early diagnosis and differentiation between different types of IMIDs. In autoimmune disorders, galectin 1 (Gal-1) is a recognized as negative immune system regulator. This study aimed to determine the possibility of using gal-1 as a diagnostic marker to differentiate between RA and PsA with polyarthritis pattern, and between PsA and Ps, and to assess its relationship with disease activity and with skin lesion. In this case-control study included 40 PsA patients with polyarthritis pattern, 40 psoriatic patients, 40 RA patients and 20 normal controls. Gal-1 levels were measured in serum and skin biopsy and disease Activity Score (DAS-ESR) was assessed. Serum gal-1 level was significantly higher in RA group in comparison to PsA, psoriatic and control. In addition, compared to the normal group, psoriatic skin lesions from PsA and Ps patients had lower levels of gal-1. Serum gal-1 levels in the RA group did not correlate with other factors such as age, disease duration, deformity, extra-articular symptoms, or DAS-ESR. Furthermore, there was no correlation between the skin's level of gal-1 and psoriatic area and severity index (PASI) score, body surface area (BSA). In conclusion, serum Gal-1 concentration may serve as a diagnostic biomarker to distinguish between RA and PsA. However, it cannot assess activity or severity of RA, and cannot differentiate psoriatic lesion either from only Ps or PsA.


Arthritis, Psoriatic , Arthritis, Rheumatoid , Psoriasis , Humans , Arthritis, Psoriatic/diagnosis , Arthritis, Psoriatic/pathology , Galectin 1 , Case-Control Studies , Immunomodulating Agents , Arthritis, Rheumatoid/diagnosis
15.
J Ultrasound Med ; 42(9): 1987-1995, 2023 Sep.
Article En | MEDLINE | ID: mdl-36880692

OBJECTIVES: Psoriatic arthritis (PsA) can mimic rheumatoid arthritis (RA) at an early stage, especially when psoriasis is lacking. In the absence of specific radiological and immunological markers, the differential diagnosis between these two diseases can be challenging. We aimed to determine whether hands ultrasonography (US) may be useful in the differential diagnosis between PsA and RA. METHODS: We conducted a cross-sectional study including patients with PsA and RA. All wrists and small joints of the hands were examined using gray-scale and Power Doppler US. The evaluated US lesions were: synovitis, tenosynovitis of extensor carpi ulnaris, extensor communis and flexor tendons, enthesitis of extensor tendons at distal interphalangeal joints, peritendon inflammation of extensor tendons, and soft tissue edema. RESULTS: Six hundred joints in 20 PsA patients and 900 joints in 30 RA patients were assessed. Extensor enthesitis was significantly more observed in PsA compared with RA (39.4 vs 26.3%, P = .006) with a significant higher frequency of enthesophytes and calcifications (P = .022 and P = .002, respectively). Peritendon inflammation of extensor digitorum tendons was observed in 13% of metacarpophalangeal joints in PsA patients versus 3% in RA patients with a significant difference (P < .001). Soft tissue edema was exclusively observed in PsA (1.5 vs 0%, P = .033). Power Doppler synovitis was significantly more frequent in RA (9.2 vs 5%, P = .002). Extensor carpi ulnaris tenosynovitis was significantly more frequent in RA (18.3 vs 2.5%, P = .017). CONCLUSION: Extrasynovial US findings may be helpful to distinguish PsA from RA especially in patients with immunonegative polyarthritis and no evidence of psoriasis.


Arthritis, Psoriatic , Arthritis, Rheumatoid , Enthesopathy , Psoriasis , Synovitis , Tenosynovitis , Humans , Arthritis, Psoriatic/diagnostic imaging , Arthritis, Psoriatic/pathology , Tenosynovitis/diagnostic imaging , Diagnosis, Differential , Cross-Sectional Studies , Arthritis, Rheumatoid/diagnostic imaging , Arthritis, Rheumatoid/pathology , Inflammation , Ultrasonography , Psoriasis/diagnosis , Edema
16.
Med Ultrason ; 25(1): 42-47, 2023 Mar 30.
Article En | MEDLINE | ID: mdl-36996392

AIM: Tenosynovitis is one of the most frequently described inflammatory lesions in psoriatic dactylitis. The aim of the study was to assess by ultrasound the distribution of content within the synovial sheath of the finger flexor tendons in a cadaveric experimental model of tenosynovitis and to describe anatomically the elements of the space between the flexor tendons and the palmar aspect of the proximal phalanx of the fingers. MATERIAL AND METHOD: Silicone was injected under ultrasound guidance into the digital flexor sheath of the index finger of a hand specimen. Ultrasound images of the distribution of the filling of the flexor synovial space with the injected material were obtained. These images were compared with images from patients with psoriatic dactylitis. The palmar regions of the hand and fingers were dissected to check the distribution of the injected silicone in the synovial cavity. Additionally, we dissected the 2nd to 5th fingers of five cadaveric hands, including the one used for the experiment. RESULTS: During the injection of the substance, we observed an increasing homogeneous hypoechoic band around the flexor tendons that differed from the images of patients. Dissection of the specimen showed the injected silicone distributed throughout the digital flexor sheath to the distal interphalangeal joint. In addition, we provided an illustrated anatomical description of the elements located between the flexor tendons and the palmar aspect of the proximal phalanx, the inflammation of which could simulate flexor tenosynovitis. CONCLUSION: The observations of this study may contribute to a better understanding of the anatomical structures involved in PsA dactylitis.


Arthritis, Psoriatic , Tenosynovitis , Humans , Tenosynovitis/diagnostic imaging , Arthritis, Psoriatic/diagnostic imaging , Arthritis, Psoriatic/pathology , Tendons/diagnostic imaging , Tendons/pathology , Fingers/diagnostic imaging , Cadaver
17.
RMD Open ; 9(1)2023 03.
Article En | MEDLINE | ID: mdl-36927849

OBJECTIVE: To investigate the influence of COVID-19 vaccination on disease activity in rheumatoid arthritis (RA) and psoriatic arthritis (PsA) patients under targeted therapies. PATIENTS AND METHODS: 1765 vaccinated patients COVID-19, 1178 (66.7%) with RA and 587 (33.3%) with PsA from the COVID-19 registry in patients with rheumatic diseases (COVIDSER) project, were included. Demographics, disease characteristics, Disease Activity Score in 28 joints (DAS28) and targeted treatments were collected. DAS28-based flare rates and categorised disease activity distribution prevaccination and post vaccination were analysed by log-linear regression and contingency analyses, respectively. The influence of vaccination on DAS28 variation as a continuous measure was evaluated using a random coefficient model. RESULTS: The distribution of categorised disease activity and flare rates was not significantly modified by vaccination. Log-linear regression showed no significant changes in the rate of flares in the 6-month period after vaccination compared with the same period prior to vaccination in neither patients with RA nor patients with PsA. When DAS28 variations were analysed using random coefficient models, no significant variations in disease activity were detected after vaccination for both groups of patients. However, patients with RA treated with Janus kinase inhibitors (JAK-i) (1) and interleukin-6 inhibitor (IL-6-i) experienced a worsening of disease activity (1.436±0.531, p=0.007, and 1.201±0.550, p=0.029, respectively) in comparison with those treated with tumour necrosis factor inhibitor (TNF-i). Similarly, patients with PsA treated with interleukin-12/23 inhibitor (IL-12/23-i) showed a worsening of disease activity (4.476±1.906, p=0.019) compared with those treated with TNF-i. CONCLUSION: COVID-19 vaccination was not associated with increased rate of flares in patients with RA and PsA. However, a potential increase in disease activity in patients with RA treated with JAK-i and IL-6-i and in patients with PsA treated with IL-12/23-i warrants further investigation.


Arthritis, Psoriatic , Arthritis, Rheumatoid , COVID-19 , Humans , Arthritis, Psoriatic/drug therapy , Arthritis, Psoriatic/pathology , Interleukin-6 , COVID-19/epidemiology , COVID-19/prevention & control , Arthritis, Rheumatoid/drug therapy , Arthritis, Rheumatoid/pathology , Interleukin-12
18.
Clin Exp Dermatol ; 48(4): 310-318, 2023 Mar 22.
Article En | MEDLINE | ID: mdl-36708030

Psoriasis is a chronic immune-mediated condition that affects the skin and joints, with current treatments still unable to offer a cure and long-term use of treatments posing health risks. Understanding the pathogenesis of the disease has helped identify new targets that have allowed for the expansion of the therapeutic arsenal. Extracellular vesicles (EVs) have recently emerged as pathophysiological mediators of psoriasis, and there have been increasing reports of EVs as potential biomarkers and therapeutics. Given their innate role as natural vehicles for cell-to-cell communication, EVs have vast potential in their ability to determine disease status based on EV-specific cargo as well as act as therapeutics because of their anti-inflammatory properties and potential for enhancement. In this review we summarize the role of EVs in the pathogenesis of psoriasis and discuss EVs as both diagnostic and therapeutic agents.


Arthritis, Psoriatic , Extracellular Vesicles , Humans , Arthritis, Psoriatic/diagnosis , Arthritis, Psoriatic/drug therapy , Arthritis, Psoriatic/pathology , Biomarkers , Extracellular Vesicles/pathology
19.
J Oral Rehabil ; 50(3): 243-255, 2023 Mar.
Article En | MEDLINE | ID: mdl-36582136

OBJECTIVES: Psoriasis is an inflammatory condition brought on by the immune system. This study aimed to perform a systematic review related to psoriatic arthritis (PsA) of the temporomandibular joint (TMJ). METHODS: The search strategy was developed by a radiologist expert with more than 20 years of experience. The search was performed without time restrictions in five electronic databases: PubMed, Web of Science, Embase, Scopus and Ovid. The search strategy was based on MeSH and Emtree terms. The methodological quality of the studies was rated using the quality assessment tools from the National Heart Lung and Blood Institute (NHLBI). RESULTS: Twenty-three publications were included, 10 being case reports. One hundred-fifty-one patients with TMJ PsA were reported. Psoriasis evolution ranged from 1.5 years to 24 years. Clinical symptoms of TMJ involvement included: TMJ pain and sounds, limited range of jaw movements, preauricular swelling, malocclusion, headache, tinnitus, neck stiffness and altered dietary function. TMJ was evaluated by magnetic resonance imaging (six studies), computed tomography (eight articles) and by ultrasonography findings (two articles). For TMJ treatment, topical and systemic medication was reported in 11 studies. Five studies included patients needing surgical procedures for TMJ ankylosis. CONCLUSIONS: A relationship between TMD and psoriasis has been revealed. TMJ PsA has been investigated and debated, although the radiographic findings or clinical symptoms of PsA are not noticeably different from other forms of TMJ arthritis. Conservative therapy can lead to significant improvement of TMJ function.


Arthritis, Psoriatic , Psoriasis , Temporomandibular Joint Disorders , Temporomandibular Joint Dysfunction Syndrome , Humans , Arthritis, Psoriatic/diagnostic imaging , Arthritis, Psoriatic/complications , Arthritis, Psoriatic/pathology , Temporomandibular Joint/pathology , Temporomandibular Joint Dysfunction Syndrome/complications , Psoriasis/complications , Psoriasis/pathology
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