scholarly journals Exploring the Diverse Immune and Genetic Landscape of Psoriatic Arthritis

2021 ◽  
Vol 10 (24) ◽  
pp. 5926
Author(s):  
Bogdan Batko

Psoriatic arthritis (PsA) is characterized by delays in diagnosis and a modest effect of treatment in terms of joint response. An understanding of molecular pathomechanisms may aid in developing diagnostic and prognostic models. Genetic susceptibility (e.g., HLA class I genes, IL-23-related genes) can be responsible for the pattern of psoriatic manifestations and affinity for tissue involvement. Gene expression analysis indicates an inflammatory profile that is distinct for PsA, but disparate across tissues. This has clinical implications, as for example, dual blockade of IL-17A and IL-17F can lead to superior clinical effects if there is differential expression of IL-17 receptors in tissues. Structural and functional impairment of barrier tissue, including host-microbiome interactions, may be the source of immune activation. Interplay between different cell populations of innate and adaptive immunity is emerging, potentially providing a link between the transition of skin-to-joint disease. Th17 subsets, IL-17A, IL-17F and IL-23 are crucial in PsA pathogenesis, with both clinical and experimental evidence suggesting a differential molecular landscape in cutaneous and articular compartments.

2018 ◽  
Vol 28 (2) ◽  
pp. 483-487
Author(s):  
Snezhina Georgieva ◽  
Dilyana Zvezdova

Psoriatic arthritis is an inflammatory joint disease associated with psoriasis vulgaris, with routinely negative rheumatoid factors and the absence of rheumatoid nodules. This is an immune-mediated disease, according to generally accepted definition of Wright and Moll from 1973. American Association against Rheumatism classified psoriatic arthritis as an independent disease in 1964. Psoriatic arthritis is a single disease with a varied clinical picture. It belongs to the group of seronegative spondyloarthropathies with which there are general clinical features. It is believed that similar mechanisms determine the onset of psoriasis and psoriatic arthritis. The clinical picture includes various clinical forms that damage the peripheral and sacroiliac joints, spine, internal organs. The treatment of psoriatic arthritis is directed simultaneously to the influence of skin and joint changes. Purpose: Our study aims to summarize our long-standing experience in the treatment of psoriatic arthritis with heliotherapy. Subject of observation: Monitoring includes 132 patients with moderate and severe form of psoriasis treated at the sanatorium in town of Pomorie for 5 years in the period 2001-2006. Results and discussion: 132 patients with psoriasis with no effect on the local therapy and have proven psoriatic arthritis were selected. In our climatic conditions, heliotherapy is appointed during the warm half-year. Sun treatment was conducted under the conditions of a healing beach, which had shielding, radiation-protective devices. In patients with erythema - pigment and pigment type skin reactivity begins with 1-2 bioadoses reached to 8-10 biodoses, carried out in the area of overcomfort. Conclusion: The studies demonstrated that heliotherapy combined with medications significantly improves the prognosis of patients with this disease. The ultimate success would mean overcoming the frequent depression conditions, better survival and social comfort for patients with psoriatic arthritis.


2018 ◽  
Vol 68 (12) ◽  
pp. 2987-2991
Author(s):  
Cristina Iordache ◽  
Bogdan Vascu ◽  
Eugen Ancuta ◽  
Rodica Chirieac ◽  
Cristina Pomirleanu ◽  
...  

Temporomandibular joint (TMJ) is commonly involved in various immune-mediated rheumatic disorders accounting for significant disability and impaired quality of life. The aim of our study was to assess inflammatory and immune parameters in patients with TMJ arthritis related to rheumatoid arthritis (RA), juvenile idiopathic arthritis (JIA), ankylosing spondylitis (AS) and psoriatic arthritis (PsA) and to identify potential relation with severity and dysfunction of TMJ pathology. We performed a cross-sectional study in a cohort of 433 consecutive RA, 32 JIA, 258 AS, and 103 PsA. Only patients presenting with clinically significant TMJ involvement (273) related to their rheumatic condition were included in the final analysis. TMJ involvement is traditionally described in chronic inflammatory rheumatic disorders, particularly in patients with higher levels of inflammation as detected in rheumatoid arthritis and psoriatic arthritis. Disease activity and severity, as well as biological and positive serological assessments (rheumatoid factor, anti-cyclic citrullinated peptide, IL-1) remain significant determinants of the severity of TMJ arthritis.


RMD Open ◽  
2021 ◽  
Vol 7 (1) ◽  
pp. e001450
Author(s):  
Clementina López-Medina ◽  
Anna Molto ◽  
Joachim Sieper ◽  
Tuncay Duruöz ◽  
Uta Kiltz ◽  
...  

ObjectivesTo characterise peripheral musculoskeletal involvement in patients with spondyloarthritis (SpA) including psoriatic arthritis (PsA), across the world.MethodsCross-sectional study with 24 participating countries. Patients with a diagnosis of axial SpA (axSpA), peripheral SpA (pSpA) or PsA according to their rheumatologist were included. The investigators were asked which diagnosis out of a list of six (axSpA, PsA, pSpA, inflammatory bowel disease-associated SpA, reactive arthritis or juvenile SpA (Juv-SpA)) fitted the patient best. Peripheral manifestations (ie, peripheral joint disease, enthesitis, dactylitis and root joint disease), their localisation and treatments were evaluated.ResultsA total of 4465 patients were included (61% men, mean age 44.5 years) from four geographic areas: Latin America (n=538), Europe plus North America (n=1677), Asia (n=975) and the Middle East plus North Africa (n=1275). Of those, 78% had ever suffered from at least one peripheral musculoskeletal manifestation; 57% had peripheral joint disease, 44% had enthesitis and 15% had dactylitis. Latin American had far more often peripheral joint disease (80%) than patients from other areas. Patients with PsA had predominantly upper limb and small joint involvement (52%).Hip and shoulder involvement was found in 34% of patients. The prevalence of enthesitis ranged between 41% in patients with axSpA and 65% in patients with Juv-SpA. Dactylitis was most frequent among patients with PsA (37%).ConclusionThese results suggest that all peripheral features can be found in all subtypes of SpA, and that differences are quantitative rather than qualitative. In a high proportion of patients, axial and peripheral manifestations coincided. These findings reconfirm SpA clinical subtypes are descendants of the same underlying disease, called SpA.


2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1325.2-1326
Author(s):  
M. Chamurlieva ◽  
E. Loginova ◽  
T. Korotaeva ◽  
Y. Korsakova ◽  
E. Gubar ◽  
...  

Background:Psoriatic arthritis (PsA) is heterogeneous in its clinical presentation and disease course, but many patients (pts) develop a destructive form of arthritis. Psoriasis (PsO) precedes arthritis by an average of 7 years. [1]. Theory of transition from PsO to PsA has been proposed recently [2]. But association between skin disease severity and joint disease are still unclear.Objectives:to evaluate association between bone erosion, PsO duration, skin and nail disease severity in PsA pts based on data from clinical practice (RU-PsART cohort).Methods:737 (M/F=350/387) PsA pts fulfilling the CASPAR criteria were included. Mean age 47.4±12.7 years (yrs), PsA duration 55[17;120] mos., PsO duration 165[74.5;292] mos., mean DAPSA 23.3[14;36.9] mos., HAQ-DI - 0.98 [0.5;1.38], CRP - 7.4 [2.1;18] mg/l. All pts underwent standard clinical examination (tender joins count (TJC)/68, swelling joints count (SJC)/66, CRP (mg/l), DAPSA, dactylitis, enthesitis by LEI + Plantar Facia (PF), HAQ-DI. Mild disease was defined as body surface area (BSA)≤10%, moderate to severe as BSA>10%. The presence/absent of nail PsO was evaluated. X-ray of feet and hand were done in 622 out of 737 pts. The one-factor model of logistic regression was used to identify a group of features that are associated with achievement MDA. M±SD, Me [Q25; Q75], Min-Max, %, t-test, Pierson-χ2, Manna-Whitney tests, ORs with 95% CI were performed. All p<0.05 were considered to indicate statistical significance.Results:PsO precedes of PsA by an average of 9.2 years. BSA≤10% was found in 615 out of 672 pts (91.5%), BSA>10% - in 57 out of 672 pts (8.5%). Nail PsO were seen in 230 out of 737 (31.2%). Bone erosion was found in 237 out of 622 of pts (38.1%). Among these pts nail PsO were seen in 67 out of 237 pts (28.3%). Enthesitis found in 236 out of 737 pts (42.1%), dactylitis – in 197 out 731 pts (27%), axial PsA – in 315 out of 731 pts (43.1%). Bone erosion significantly associated with PsO duration more than 5 yrs., skin and nail PsO severity, high PsA activity by DAPSA, axial manifestation and duration of PsA > 36 mos. (Figure 1).Figure 1Forest plot of factors associated with bone erosion in PsA pts.Conclusion:In our cohort the majority of PsA pts had mild PsO preceded PsA on average of 9.2 yrs. Bone erosion was found in 30% of PsA pts which associated with PsO duration, skin and nail disease severity as well as with PsA activity. Early diagnosis and therapeutic intervention within a “window of opportunity” are very important for improving outcomes and prevent structural damage in PsA.References:[1]Tillett W, et al. Interval between onset of psoriasis and psoriatic arthritis comparing the UK Clinical Practice Research Datalink with a hospital-based cohort. Rheumatol. 2017; 56, 2109–2113[2]Scher JU, et al. Preventing psoriatic arthritis: focusing on patients with psoriasis at increased risk of transition. Nat Rev Rheumatol. 2019;15(3):153-166. doi: 10.1038/s41584-019-0175-0. PMID: 30742092.Disclosure of Interests:None declared.


2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1038.1-1038
Author(s):  
M. S. Chimenti ◽  
C. Ciccacci ◽  
G. De Benedittis ◽  
A. Latini ◽  
P. Conigliaro ◽  
...  

Background:Psoriatic arthritis (PsA) is a chronic inflammatory joint disease typically associated with psoriasis and classified in the group of spondyloarthritis (1). The pathogenesis is based on an interplay of different genes interacting with several environmental factors including stress, trauma, infections, triggering an inflammatory response related to the activation of innate and acquired immunity in different tissues and organs (2). However, the risk for the development of PsA is not clearly understood.Objectives:The aim of this study was to evaluate, in a cohort of Italian PsA out-patients of the Rheumatology Unit of the University of Rome Tor Vergata, the association of genetic variants in candidate genes for PSA susceptibility and their possible contribute in the modulation of clinical and laboratory features.Methods:The genes were selected according to previous studies describing these genes as involved in susceptibility to rheumatoid arthritis (RA) (3), since a common genetic background can be shared between these diseases. Nine SNPs (single nucleotide polymorphism) in eight candidate genes were analysed: STAT4 (rs7574865), TRAF3IP2 (rs33980500), TNFAIP3 (rs6920220 and rs2230926), MIR146A (rs2910164), PSORS1C1 (rs2233945), IL-10 (rs1800872), HCP5 (rs3099844) and ERAP1 (rs27524). Polymorphisms were analysed in 163 consecutive PsA out-patients and 198 healthy controls (HC). Genotyping was performed by allelic discrimination by TaqMan assay. Alleles frequencies differences between cases and controls or between phenotypic groups were compared using Pearson’s χ 2 test.Results:We have observed an association between PSA susceptibility and the variant alleles of STAT4 [OR= 1.60 (1.15-2.21), P= 0.005], TRAF3IP2 [OR= 1.65 (1.01-2.65), P= 0.04], ERAP1 [OR= 1.40 (1.05-1.85), P= 0.02] and TNFAIP3 (rs6920220) [OR= 1.75 (1.19-2.57), P= 0.004]. On the contrary, the variant allele of IL-10 polymorphism seems to play a protective role [OR= 0.74 (1.05-1.85), P= 0.05]. Moreover, in order to define a genetic risk profile, we have counted the total number of risk alleles in each subject, considering as risk alleles the allelic variant of rs7574865 (STAT4), rs33980500 (TRAF3IP2), rs6920220 (TNFAIP3) and rs27524 (ERAP1) SNPs. Then, we have compared the risk allele number distribution between patients and HC (Fig.1). Classes with 3 or more risk alleles are significantly more represented in patients than in HC (OR= 2.03, P=0.004). The risk to develop the disease increases significantly in subjects with at least four risk alleles (OR= 2.96, P=0.002).Figure 1.Number of risk alleles in patients and controls: rs7574865 (STAT4), rs33980500 (TRAF3IP2), rs6920220 (TNFAIP3) and rs27524 (ERAP1) SNPs.Conclusion:We confirm the associations between five SNPs, already studied in RA, and PSA susceptibility, suggesting a common inflammatory pathway in chronic inflammatory rheumatological diseases. Moreover, we show how the genotyping of only few associated SNPs could help to define a genetic risk profile for PSA development.References:[1]Calabresi E, et al. One year in review 2019: psoriatic arthritis. Clin Exp Rheumatol. 2020;38:1046-55.[2]Chimenti MS, Triggianese P, De Martino E, Conigliaro P, Fonti GL, Sunzini F, Caso F, Perricone C, Costa L, Perricone R. An update on pathogenesis of psoriatic arthritis and potential therapeutic targets. Expert Rev Clin Immunol. 2019 Aug;15(8):823-836.[3]Ciccacci C, et al. Polymorphisms in STAT-4, IL-10, PSORS1C1, PTPN2 and MIR146A genes are associated differently with prognostic factors in Italian patients affected by rheumatoid arthritis. Clin Exp Immunol. 2016;186:157-63.Disclosure of Interests:None declared


2004 ◽  
Vol 50 (3) ◽  
pp. P55 ◽  
Author(s):  
Bernard S. Goffe ◽  
Alice Gottlieb ◽  
Mark Lebwohl ◽  
Ralph Zitnik

F1000Research ◽  
2016 ◽  
Vol 5 ◽  
pp. 2670 ◽  
Author(s):  
Dafna D. Gladman

This article reviews recent advances in psoriatic arthritis (PsA) over the past several years with emphasis on early diagnosis, better understanding of pathogenesis, and new therapeutic approaches. Early diagnosis is important, since people who present late do not fare as well. There are a number of clinical, laboratory, and ultrasound features that can help identify patients destined to develop PsA, and several screening tools have been developed. It is recognized that genetic and epigenetic factors, as well as T cells and cytokines, play a role in the pathogenesis of PsA, and several targets have been identified for therapeutic interventions. New therapies have been developed and tested in PsA and have been found to be highly effective for both skin and joint manifestations of the disease. The expectation is that, in the future, PsA patients will be treated early and more aggressively and that there will not be significant progression of joint damage. Moreover, with effective treatment of the skin and joint disease and management of risk factors for the comorbidities, we can expect to reduce their occurrence and further reduce the excess mortality and reduced quality of life and function in these patients.


RMD Open ◽  
2018 ◽  
Vol 4 (2) ◽  
pp. e000765 ◽  
Author(s):  
Silva Pukšić ◽  
Pernille Bolton-King ◽  
Joseph Sexton ◽  
Brigitte Michelsen ◽  
Tore K Kvien ◽  
...  

ObjectivesDisease Activity index for PSoriatic Arthritis (DAPSA) (sum score 68/66 tender/swollen joint counts (68TJC/66SJC), patient’s global assessment, pain and C-reactive protein (CRP)) is recommended for clinical assessment of disease activity in patients with psoriatic arthritis (PsA). Ultrasound (US) (grey scale (GS) and power Doppler (PD)) detects inflammation in joints and extra-articular structures. The present objectives were to explore the longitudinal relationships between DAPSA, clinical assessment as well as patient-reported outcome measures (PROMs) with US in patients with PsA initiating biological DMARDs and the associations between DAPSA and US remission.Methods47 patients with PsA were examined at baseline and after 3, 6, 9 and 12 months. Assessments included 68TJC/66SJC, examiner’s global assessment (EGA), PROMs, CRP, erythrocyte sedimentation rate (ESR) and US GS and PD (48 joints, 10 flexor tendons, 14 entheses, 4 bursae). Clinical composite scores and PD sum scores (0=remission) were calculated. Longitudinal associations were explored by generalised estimating equations with linear and logistic regression.ResultsDAPSA was not longitudinally associated to PD. 66SJC, ESR, 28-joint Disease Activity Score, EGA and CRP were longitudinally associated with PD (p<0.001–0.03), whereas the pain-related components of DAPSA (68TJC and pain) as well as PROMs were not associated. At 6–12 months, remission was achieved in 29%–33 % of the patients for DAPSA and 59%–70 % for PD. The association between DAPSA and PD remission was not significant (p=0.33).ConclusionsDAPSA was not associated with US inflammatory findings which indicates that DAPSA and US may assess different aspects of PsA activity.


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