Differences in Osteoimmunological Biomarkers Predictive of Psoriatic Arthritis among a Large Italian Cohort of Psoriatic Patients.
Diani Marco,Perego Silvia,Sansoni Veronica,Bertino Lucrezia,Gomarasca Marta,Faraldi Martina,Pigatto Paolo Daniele Maria,Damiani Giovanni,Banfi Giuseppe,Altomare Gianfranco,Lombardi Giovanni
International journal of molecular sciences
(1) Background: In literature it is reported that 20-30% of psoriatic patients evolve to psoriatic arthritis over time. Currently, no specific biochemical markers can either predict progression to psoriatic arthritis or response to therapies. This study aimed to identify osteoimmunological markers applicable to clinical practice, giving a quantitative tool for evaluating pathological status and, eventually, to provide prognostic support in diagnosis. (2) Methods: Soluble (serum) bone and cartilage markers were quantified in 50 patients with only psoriasis, 50 psoriatic patients with psoriatic arthritis, and 20 healthy controls by means of multiplex and enzyme-linked immunoassays. (3) Results: Differences in the concentrations of matrix metalloproteases (MMPs), tissue inhibitors of metalloproteinases (TIMPs), receptor activator of nuclear factor kappa-B- ligand (RANK-L), procollagen type I N propeptide (PINP), C-terminal telopeptide of type I collagen (CTx-I), dickkopf-related protein 1 (DKK1), and sclerostin (SOST) distinguished healthy controls from psoriasis and psoriatic arthritis patients. We found that MMP2, MMP12, MMP13, TIMP2, and TIMP4 distinguished psoriasis from psoriatic arthritis patients undergoing a systemic treatment, with a good diagnostic accuracy (Area under the ROC Curve (AUC) > 0.7). Then, chitinase-3-like protein 1 (CHI3L1) and MMP10 distinguished psoriasis from psoriatic arthritis not undergoing systemic therapy and, in the presence of onychopathy, MMP8 levels were higher in psoriasis than in psoriatic arthritis. However, in these latter cases, the diagnostic accuracy of the identified biomarkers was low (0.5 < AUC < 0.7). (4) Conclusions. By highlighting never exploited differences, the wide osteoimmunological biomarkers panel provides a novel clue to the development of diagnostic paths in psoriasis and psoriasis-associated arthropathic disease.
Nail involvement as a predictor of concomitant psoriatic arthritis in patients with psoriasis.
Langenbruch A,Radtke M A,Krensel M,Jacobi A,Reich K,Augustin M
The British journal of dermatology
BACKGROUND:Patients with psoriatic arthritis (PsA) suffer from increased burden of disease and impairments in quality of life. Early detection and treatment of PsA could contribute to the prevention of clinical and radiological progression. OBJECTIVES:To analyse the predictive value of clinical and patient-reported outcomes for concomitant PsA in a population-based cohort of patients with psoriasis. METHODS:We performed a retrospective analysis of data from three independent national cross-sectional studies on health care in psoriasis and PsA, conducted in Germany in the years 2005, 2007 and 2008. Patients with psoriasis were included in the study by dermatologists (n = 3520) and via the German patient advocacy group for psoriasis (n = 2449). In all studies, psoriasis history, clinical findings, PsA, nail involvement, health care and patient-reported outcomes were collected with standardized questionnaires. RESULTS:In the regression model on 4146 patients the strongest predictors for concomitant PsA were nail involvement [odds ratio (OR) 2·93, 95% confidence interval (CI) 2·51-3·42, P < 0·001] and inpatient hospital treatment (OR 1·63, 95% CI 1·38-1·93, P < 0·001). By contrast, scalp involvement was not a significant predictor. CONCLUSIONS:Patients with psoriasis seen by dermatologists and those in patient advocacy groups show clinical indicators of PsA, the most predictive being nail disease. In practice, a comprehensive assessment of clinical findings associated with PsA is needed.
Assessment of Response to Treatment, Remission, and Minimal Disease Activity in Axial Psoriatic Arthritis Treated with Tumor Necrosis Factor Inhibitors.
Lubrano Ennio,Parsons Wendy J,Perrotta Fabio Massimo
The Journal of rheumatology
OBJECTIVE:To assess the response to treatment, remission, and minimal disease activity (MDA) in a group of patients with predominant axial psoriatic arthritis (axPsA). Predictors of response were also evaluated. METHODS:Patients fulfilling the ClASsification of Psoriatic ARthritis (CASPAR) criteria and treated with anti-tumor necrosis factor (anti-TNF) agents adalimumab, etanercept, and golimumab were enrolled and prospectively followed every 4 months for 1 year in a clinical practice setting. Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) 50 was assessed as a set of response criteria to treatment; Composite Psoriatic Disease Activity Index (CPDAI) < 4, Disease Activity Index for Psoriatic Arthritis (DAPSA) score ≤ 3.3, and partial remission (PR) were also evaluated as remission criteria. Patients were considered in MDA when they met at least 5/7 of the criteria previously defined. Patients achieving BASDAI 50, PR, and MDA were compared to identify outcome predictor factors. Concordance between the outcome measures was also performed. RESULTS:Of the 58 patients treated with anti-TNF, at baseline no patients were in PR or MDA. No patients had a CPDAI < 4 or a DAPSA score ≤ 3.3. After 12 months, BASDAI 50 was achieved in 15/48 patients (31.2%). CPDAI < 4, DAPSA score ≤ 3.3, PR, and MDA were achieved, respectively, in 17/48 (35.4%), 11/48 (22.9%), 11/48 (22.9%), and 24/48 (50%) patients. No difference was found among the 3 anti-TNF. Predictors for MDA were male sex, young age, low disease duration, low Health Assessment Questionnaire score, and absence of enthesitis. CONCLUSION:This longitudinal observational study, based on a clinical practice setting, showed that remission and MDA are achievable targets in axPsA treated with anti-TNF. Predictors of remission and MDA were also identified.
Is Obesity a Predictor for Lack of Response to Treatment in Psoriatic Arthritis? A Systematic Review.
Gratacós Jordi,Galíndez Eva,Otón Teresa
OBJECTIVES:To update the study of the association between obesity and treatment response in psoriatic arthritis. METHODS:Updating a systematic review of clinical trials, prospective or retrospective longitudinal studies and case-control studies in psoriatic arthritis in which obesity was assessed as a predictor of efficacy or toxicity. Risks of bias were assessed with validated scales. A meta-analysis of the results of studies with similar outcome variables and weight measurements was performed. RESULTS:Twenty-one studies were included (6 review of clinical trials, 6 longitudinal studies, 7 registers and one case-control studie), with moderate quality. The risk of achieving an ACR20 response if weight≥100kg was estimated at OR=1.42 (1-2.08) and that of withdrawing treatment in an OR of 1.60 (95% CI: 1.34 - 1.92). CONCLUSIONS:There seems to be a greater risk of withdrawal of treatment due to inefficacy and difficulty in achieving remission in patients with psoriatic arthritis if they are obese.
Nail psoriasis as a predictor of the development of psoriatic arthritis.
Raposo I,Torres T
Psoriatic arthritis is a psoriasis-related spondyloarthropathy that occurs in 20-30% of patients with psoriasis. Various imaging studies have demonstrated that there is a considerable proportion of undiagnosed psoriatic arthritis among patients with psoriasis. Since early detection and treatment of psoriatic arthritis could, ultimately, allow the prevention of clinical and radiologic progression of the disease, there is the need to establish clinical indicators to detect this risk. Nail psoriasis has been proposed as a predictor for the development of psoriatic arthritis. The inflammation involving the entheses, called enthesitis, is an early inflammatory change seen in psoriatic arthritis, and nail changes appear to result from the close relationship between the nail and the enthesis of the distal interphalangeal extensor tendon, one of the main entheseal compartments affected in psoriatic arthritis. As skin lesions precede articular symptoms in more than 75-80% of patients with psoriatic arthritis, dermatologists may play a key role in the early detection and management of psoriatic arthritis.
Serum-based soluble markers differentiate psoriatic arthritis from osteoarthritis.
Chandran Vinod,Abji Fatima,Perruccio Anthony V,Gandhi Rajiv,Li Suzanne,Cook Richard J,Gladman Dafna D
Annals of the rheumatic diseases
OBJECTIVES:We aimed to identify soluble biomarkers that differentiate psoriatic arthritis (PsA) from osteoarthritis (OA). METHODS:Markers of cartilage metabolism (cartilage oligomeric matrix protein [COMP], hyaluronan), metabolic syndrome (adiponectin, adipsin, resistin, hepatocyte growth factor [HGF], insulin, leptin) and inflammation (C-reactive protein [CRP], interleukin-1β [IL-1β], IL-6, IL-8, tumour necrosis factor alpha [TNFα], monocyte chemoattractant protein-1 [MCP-1], nerve growth factor [NGF]) were compared in serum samples from 201 patients with OA, 77 patients with PsA and 76 controls. Levels across the groups were compared using the Kruskal-Wallis test. Pairwise comparisons were made with Wilcoxon rank-sum test. Multivariate logistic regression analyses were performed to identify markers that differentiate PsA from OA. Receiver operating characteristic (ROC) curves were constructed based on multivariate models. The final model was further validated in an independent set of 73 PsA and 75 OA samples using predicted probabilities calculated with coefficients of age, sex and biomarkers. RESULTS:Levels of the following markers were significantly different across the three groups (p<0.001)-COMP, hyaluronan, resistin, HGF, insulin, leptin, CRP, IL-6, IL-8, TNFα, MCP-1, NGF. In multivariate analysis, COMP (OR 1.24, 95% CI 1.06 to 1.46), resistin (OR 1.26, 95% CI 1.07 to 1.48), MCP-1 (OR 1.10, 95% CI 0.07 to 1.48) and NGF (OR<0.001, 95% CI <0.001 to 0.25) were found to be independently associated with PsA versus OA. The area under the ROC curve (AUROC) for this model was 0.99 compared with model with only age and sex (AUROC 0.87, p<0.001). Similar results were obtained using the validation sample. CONCLUSION:A panel of four biomarkers may distinguish PsA from OA. These results need further validation in prospective studies.
The role of imaging in early diagnosis and prevention of joint damage in inflammatory arthritis.
Yue Jiang,Wu Dongze,Tam Lai-Shan
Expert review of clinical immunology
INTRODUCTION:Inflammatory arthritis is characterized by chronic inflammation in the synovium, associated with degradation of cartilage and erosion of juxta-articular bone. The bone loss and joint destruction mediated by aberrant immunological responses resulting in proinﬂammatory cytokine release and various immune cell activation are known as osteoimmunology. Areas covered: A structured literature search including Medline and PubMed, Cochrane meta-analyses and abstracts of international congresses was performed to review joint damage in inflammatory arthritis in terms of pathogenesis, novel imaging assessment, and prevention. Expert commentary: Deeper understanding of the integration of the skeletal and immune as well as inflammatory system is paving the way to prevent bone loss and bone destruction in inflammatory arthritis. With the availability of various imaging modalities such as ultrasound, magnetic resonance imaging (MRI) and high-resolution peripheral quantitative computed tomography (HR-pQCT), we are now able to detect early joint damage, early diagnosis of inflammatory arthritis, monitor the progression or even ascertain whether the inflammatory process is effectively suppressed to allow repair of joint damage by novel therapeutic agents.
Biomarkers to Diagnose Early Arthritis in Patients With Psoriasis.
Chiu Ya-Hui Grace,Ritchlin Christopher T
BACKGROUND:Psoriatic arthritis is a potentially destructive, inflammatory joint disease that affects 20% to 30% of patients with psoriasis. Psoriasis precedes the onset of joint inflammation by approximately 10 years, providing a unique opportunity to intervene and prevent or delay onset of musculoskeletal manifestations. The emergence of sensitive imaging modalities and cellular biomarkers may facilitate early identification of patients with psoriasis who have subclinical joint disease and might help stratify patients with an early onset of arthritis. METHODS:The translational studies described herein are focused on the development of cellular biomarkers identified with flow cytometry and cell culture techniques in patients with psoriasis and psoriatic arthritis. RESULTS AND CONCLUSION:The combination of power Doppler ultrasound imaging and cellular biomarkers (ie, CD16 and dendritic cell specific transmembrane protein) to diagnose early psoriatic arthritis and to stratify patients with established psoriatic arthritis provides a new opportunity to optimize treatment outcomes in this potentially disabling disease.
The role of ultrasound in the diagnosis and management of psoriatic arthritis.
Current rheumatology reports
Psoriatic arthritis (PsA) presents many diagnostic, management and research challenges for rheumatologists who wish to obtain early diagnosis, differentiate synovitis and enthesitis, monitor disease activity accurately and objectively, prevent the development of structural damage, deliver local therapy accurately, and obtain PsA tissue for research purposes. Musculoskeletal ultrasound (MSUS) is widely used by European rheumatologists in their clinical practice to meet these challenges and has the potential to become the rheumatologist's stethoscope in Europe and North America. This paper examines the evidence that MSUS can improve clinical evaluation of patients with PsA for synovitis and enthesitis, that MSUS is more sensitive than plain radiography in detecting structural damage in joints, that MSUS can improve the success of joint aspiration and guide biopsy of PsA tissues. Recent exciting developments in the management of PsA are detailed including the role of power Doppler in the diagnosis of enthesitis in PsA, the role of MSUS in objective monitoring of disease activity, the evaluation of MSUS in the diagnosis of sacroiliitis, and the use of MSUS to guide therapeutic injection of the sacroiliac joints.
Soluble biomarkers may differentiate psoriasis from psoriatic arthritis.
The Journal of rheumatology. Supplement
Patients with psoriatic arthritis (PsA) have a higher inflammatory burden and poorer quality of life compared to patients with psoriasis without PsA. Early identification of PsA may prevent joint damage progression and improve quality of life. Soluble biomarkers have the potential to be useful for screening patients with psoriasis for underlying PsA so that appropriate referral to a rheumatologist is made. Pilot studies have shown that C-reactive protein, interleukin 6, cartilage oligomeric matrix protein (COMP), Dickkopf-1, and macrophage-colony stimulating factor may differentiate PsA from psoriasis without PsA. Compared with controls, increased serum levels of receptor activator of nuclear factor-κB ligand, tumor necrosis factor superfamily member 14, matrix metalloproteinase-3 (MMP-3), and COMP are independently associated with psoriatic disease. Increased levels of high-sensitivity CRP (hsCRP), osteoprotegerin (OPG), MMP-3, and the ratio of C-propeptide of type II collagen (CPII) to collagen fragment neoepitopes Col2-3/4 C(long mono) (C2C) are independently associated with PsA. A combination of hsCRP, OPG, MMP-3, and the ratio CPII of C2C was able to distinguish patients with PsA from those with psoriasis alone in a receiver-operating characteristic curve analysis, with area under the curve 0.904. Therefore, a combination of the above biomarkers may at least have a role in screening patients with psoriasis for PsA. These findings need to be validated in prospective studies.
Early biomarkers of joint damage in rheumatoid and psoriatic arthritis.
Mc Ardle Angela,Flatley Brian,Pennington Stephen R,FitzGerald Oliver
Arthritis research & therapy
Joint destruction, as evidenced by radiographic findings, is a significant problem for patients suffering from rheumatoid arthritis and psoriatic arthritis. Inherently irreversible and frequently progressive, the process of joint damage begins at and even before the clinical onset of disease. However, rheumatoid and psoriatic arthropathies are heterogeneous in nature and not all patients progress to joint damage. It is therefore important to identify patients susceptible to joint destruction in order to initiate more aggressive treatment as soon as possible and thereby potentially prevent irreversible joint damage. At the same time, the high cost and potential side effects associated with aggressive treatment mean it is also important not to over treat patients and especially those who, even if left untreated, would not progress to joint destruction. It is therefore clear that a protein biomarker signature that could predict joint damage at an early stage would support more informed clinical decisions on the most appropriate treatment regimens for individual patients. Although many candidate biomarkers for rheumatoid and psoriatic arthritis have been reported in the literature, relatively few have reached clinical use and as a consequence the number of prognostic biomarkers used in rheumatology has remained relatively static for several years. It has become evident that a significant challenge in the transition of biomarker candidates to clinical diagnostic assays lies in the development of suitably robust biomarker assays, especially multiplexed assays, and their clinical validation in appropriate patient sample cohorts. Recent developments in mass spectrometry-based targeted quantitative protein measurements have transformed our ability to rapidly develop multiplexed protein biomarker assays. These advances are likely to have a significant impact on the validation of biomarkers in the future. In this review, we have comprehensively compiled a list of candidate biomarkers in rheumatoid and psoriatic arthritis, evaluated the evidence for their potential as biomarkers of bone (joint) damage, and outlined how mass spectrometry-based targeted and multiplexed measurement of candidate biomarker proteins is likely to accelerate their clinical validation and the development of clinical diagnostic tests.
Prevalence and clinical features of psoriatic arthritis in psoriasis patients in Spain. Limitations of PASE as a screening tool.
López Estebaránz Jose Luis,Zarco-Montejo Pedro,Samaniego M Luz,García-Calvo Carmen,
European journal of dermatology : EJD
BACKGROUND:Diagnosing and initiating treatment of psoriatric arthritis (PsA) as early as possible is essential to prevent irreversible joint destruction and poor clinical outcomes. Dermatologists are uniquely placed to identify early symptoms of PsA in psoriasis patients but levels of under- and late-diagnosis remain high. OBJECTIVE:To evaluate the prevalence and clinical features of PsA in Spanish psoriatic patients attended by dermatologists and then referred to rheumatologic units for PsA diagnosis confirmation. METHODS:a multicenter, non-interventional, cross-sectional trial conducted at 40 hospitals in Spain. Patients were initially screened for PsA by a dermatologist based on clinical evaluation and results from the Psoriatic Arthritis Screening and Evaluation (PASE) Questionnaire. All patients were then evaluated by a blinded rheumatologist for the presence of PsA using Moll and Wright criteria and Classification Criteria for Psoriatic Arthritis (CASPAR). RESULTS:Of 375 psoriatic patients enrolled at dermatology units, 28.6% patients scored ≥44 in PASE, whereas 32.3% patients screened positive for suspicion of PsA (clinical evaluation and/or PASE). Correlation of suspicion of PsA by dermatologists and PASE score was 0.368 (Pearson correlation coefficient). Following rheumatologic assessment, prevalence of PsA was 22.9% (86/375 patients) according to Moll and Wright and CASPAR criteria. The correlation of diagnosis of PsA between dermatologists and rheumatologists was 0.410 (Kappa Index). CONCLUSIONS:Prevalence of PsA in our study was within the range reported in other studies. Our analyses found only a moderate correlation in the diagnosis of PsA between dermatologists and rheumatologists. The screening questionnaire, PASE, showed a moderate predictive value for the diagnosis of PsA.
The pathogenesis of psoriatic arthritis.
Veale Douglas J,Fearon Ursula
Lancet (London, England)
Psoriatic arthritis is a chronic, immune-mediated, inflammatory arthropathy that presents with inflammation of the joints and entheses, including those of the axial skeleton, and is associated with increased mortality from cardiovascular disease. Diagnosis is primarily based on clinical phenotype because of the diversity of the associated features, which can include skin and nail disease, dactylitis, uveitis, and osteitis. Improved understanding of the pathogenesis of psoriatic arthritis has led to the development of effective biologics and small-molecular drugs targeting specific cytokines and signalling pathways, which can prevent disease progression and improve quality of life. However, at least 40% of patients with psoriatic arthritis have only a partial response or fail to respond to such treatments. Cytokine inhibitors, mainly those specific for tumour necrosis factor and, more recently, the interleukin 23-T-helper-17 cell pathway, have been highly successful in the treatment of disease manifestations in several different tissues, although targeting the interleukin 23-T-helper-17 cell pathway might be more effective in psoriasis than in arthritis. However, the precise mechanisms underlying the pathogenesis of psoriatic arthritis-which include genetics, environmental factors, and immune-mediated inflammation-are complex, and the relationship between disease of the joint and that of other domains is poorly understood. Improving our understanding of psoriatic arthritis pathogenesis could help to establish validated biomarkers for diagnosis, predict therapeutic response and remission, develop precision medicines, and predict which patients will respond to which therapy. We discuss advances in pathogenetic translational research that could inform these issues.
Emerging molecular biomarkers for predicting therapy response in psoriatic arthritis: A review of literature.
Pouw Juliëtte,Leijten Emmerik,Radstake Timothy,Boes Marianne
Clinical immunology (Orlando, Fla.)
Psoriatic arthritis (PsA) is a heterogeneous, chronic inflammatory musculoskeletal disorder that affects ~0.1% of the population. PsA may severely impact quality-of-life and constitutes a significant economic burden on our health care system. While early effective treatment is deemed essential to prevent irreversible joint damage and functional impairment, not all patients respond to the same disease modifying anti-rheumatic drugs (DMARDs). DMARD options for PsA are rapidly evolving, yet only 50-60% of patients show a satisfactory response to their first-line DMARD therapy. Hence, there is an urgent medical need to predict which patients benefit from a particular treatment. To this end, molecular biomarkers capable of predicting therapeutic response are currently being scrutinized in clinical studies, that together should build a framework for clinical guidelines that improve personalized targeted treatment. In this review new developments within the field of biomarker discovery for predicting therapeutic response to DMARDs in PsA are examined.
Biomarkers for rheumatoid and psoriatic arthritis.
Verheul M K,Fearon U,Trouw L A,Veale D J
Clinical immunology (Orlando, Fla.)
Rheumatic diseases, such as rheumatoid and psoriatic arthritis are systemic inflammatory conditions characterized by a chronic form of arthritis, often leading to irreversible joint damage. Early treatment for patients with rheumatic diseases is required to reduce or prevent joint injury. However, early diagnosis can be difficult and currently it is not possible to predict which individual patient will develop progressive erosive disease or who may benefit from a specific treatment according to their clinical features at presentation. Biomarkers are therefore required to enable earlier diagnosis and predict prognosis in both rheumatoid arthritis and psoriatic arthritis. In this review we will examine the evidence and current status of established and experimental biomarkers in rheumatoid and psoriatic arthritis for three important purposes; disease diagnosis, prognosis and prediction of response to therapy.
Verna Wright Lecture: Psoriatic Arthritis: The Need for Early Intervention.
McHugh Neil J
The Journal of rheumatology. Supplement
About 30% of individuals with skin psoriasis will develop an inflammatory disease of the peripheral or axial skeleton involving synovial and/or entheseal tissue termed psoriatic arthritis (PsA). In most cases psoriasis will precede PsA by several years. Hence skin psoriasis provides an opportune model to investigate genetic and environmental factors that interact and contribute to the development of a common form of inflammatory arthritis. Further, the preexisting presence of psoriasis represents a unique opportunity for the early detection of arthritis and the potential for more effective intervention. However, despite the presence of psoriasis, there may be delay in the diagnosis of PsA that is associated with adverse longterm outcome. Undiagnosed disease is not uncommon, as demonstrated by studies applying screening questionnaires to primary care and dermatology clinic populations. Other potential risk factors, such as obesity and smoking, the presence of certain genetic and biomarker profiles, combined with accurate imaging modalities, offer the potential for more targeted screening. So in future it should be possible to detect PsA at a much earlier stage and prevent significant joint damage and associated disability before it happens.
MIG in psoriatic arthritis.
La Clinica terapeutica
Monokine induced by interferon (IFN)-γ (MIG) / chemokine (C-X-C motif) ligand 9 (CXCL)9 is involved in the pathogenesis of psoriatic arthritis (PsA). It was demonstrated that both blood plasma-derived dendritic cells (pDCs) and pDCs isolated from rheumatoid arthritis (RA) and PsA synovial fluid (SF), expressed CXC receptor (R) 3 and CXCR4, and that the chemotaxis of blood-derived pDCs is stimulated by MIG, (IFN)-γ-inducible protein 10 (IP-10)/CXCL10, IFN-inducible T-cell α chemoattractant (I-TAC) )/CXCL11 and stromal cell-derived factor 1 (SDF-1)/ CXCL12, present in RA and PsA SF. In PsA patients have been found a Th1 immune predominance at early stage of disease, while a reduction of these chemokines has been observed in long lasting PsA, with a significant increase of monocyte chemoattractant protein-1/IP-10 ratio. This suggest a shift from Th1 to the Th2 immune response in long lasting PsA. High levels of MIG has been found in patients with PsA and autoimmune thyroiditis too. This chemokine has been proposed as a useful marker to monitor the activity as well the progression of PsA. Efforts have been made to modulate or prevent the production of MIG in PsA aiming to alter the course of the disease.
Preventing psoriatic arthritis: focusing on patients with psoriasis at increased risk of transition.
Scher Jose U,Ogdie Alexis,Merola Joseph F,Ritchlin Christopher
Nature reviews. Rheumatology
Psoriasis is one of the most common chronic inflammatory skin diseases, affecting 3% of the world's population, and approximately one-third of patients with psoriasis will eventually transition to having psoriatic arthritis (PsA). The evolution from cutaneous to synovio-entheseal inflammation in these patients presents an opportunity to investigate the critical events linked to arthritis development. The events responsible for progression to PsA are currently unclear. Genetic and clinical-demographic risk factors (most notably familial aggregation and psoriasis sub-phenotypes) provide relevant insights into the variables that promote transition. The specific underlying molecular and cellular mechanisms, however, remain poorly defined. Intriguingly, although targeting the IL-23-IL-17 axis substantially improves psoriasis outcomes, this strategy is not more effective than TNF inhibitors in improving musculoskeletal symptoms in PsA. Major unmet needs in the field of PsA include defining those patients with psoriasis at increased risk of developing arthritis, improving our understanding of the natural history of disease and characterizing the immune, environmental and molecular subclinical events preceding PsA onset. Improving our knowledge of this transition is essential for designing clinical trials with treatments that can delay, attenuate or even prevent the development of PsA in patients with psoriasis.