Psoriatic Arthritis

Psoriatic arthritis ( PA) is a heterogeneous condition with musculoskeletal involvement that manifests with diverse symptoms such as arthritis, dactylitis, enthesitis and axial involvement. In addition to musculoskeletal symptoms, up to 30% of patients have coexisting psoriasis or nail disease.

Psoriatic arthritis (PsA) was first defined by Moll and Wright in the 1970s as “inflammatory arthritis in the presence of psoriasis with the usual absence of rheumatoid factor . ” Although almost 50 years have passed since the first clinical description, diagnosis remains a challenge for clinicians due to the lack of validated diagnostic criteria, the heterogeneous nature of the condition, and poor identification of the disease, particularly in patients vulnerable.

Currently, diagnosis is based on the identification of clinical signs and symptoms, evaluated in multiple domains, based on classification criteria. Although the developed classification criteria have been well validated in established disease, there is still a need for early identification through the use of diagnostic biomarkers.

In recent years, pharmacological treatments for PA have expanded exponentially, although long-term therapeutic effects are largely based on clinical experience and not extensive analysis based on head-to-head trials. Over the past two decades, symptomatic treatments have evolved from traditional disease-modifying antirheumatic drugs (DMARDs) to targeted biological therapies.

Although the development of biologic therapies has revolutionized the treatment of PA and improved outcomes, predicting and measuring therapeutic outcomes in patients remains a challenge. On the other hand, there is a growing consensus that it is possible to identify and treat the disease before clinical characteristics develop, which would enable early intervention with the aim of preventing the disease.

The reported prevalence of psoriatic arthritis (PsA) worldwide is 0.3% to 1% although studies conducted around the world often have significant differences, reflecting methodological differences, including variations in the classifications used, use of incorrect coding and diagnosis algorithms, using low sensitivity criteria such as those defined by the regulations of the European Spondyloarthropathy Study Group . These factors make it very difficult to compare differences in prevalence between studies. Despite significant advances in understanding the pathophysiology of PA in recent decades, diagnosis remains problematic.

It is estimated that almost 50% of cases in primary and secondary care clinics are unrecognized.

There are no diagnostic criteria available for PA. The Classification of Psoriatic ARthritis (CISPAR) criteria were developed in 2006 to help standardize the inclusion of a homogeneous patient population in trials, and have been well demonstrated to have high sensitivity and specificity. However, classification criteria favor specificity over sensitivity and do not provide diagnosis. Patients often experience a “diagnostic odyssey,” with delays in disease identification and subsequent prompt referral to secondary care.

Inflammatory markers such as C-reactive protein and erythrocyte sedimentation rate are normal in almost 50% of patients.

Currently, no serum biomarkers have been identified that can correlate with the diagnosis. A recent study retrospectively analyzed serological markers and comorbidities in 629 patients with psoriasis, including 102 with PsA.

Various serological markers were analyzed, including anti-extractable nuclear antigen, antiphospholipid and antineutrophil cytoplasmic autoantibodies, as well as hematological and inflammatory parameters. No serological marker was able to distinguish patients with AP, although interestingly, certain comorbidities were more prevalent in the population with AP. Other studies have examined the potential role of chemokines as diagnostic biomarkers.

In 2016, Abji et al. reported that CXCL10 levels are elevated in patients who develop Psoriasis compared to those with psoriasis without Psoriasis at baseline. In 2020, the same group showed that CXCL10 levels fall after the onset of arthritis. The authors suggested that their findings warrant further investigating the predictive value of CXCL10 in the diagnosis of AP. Ultimately, they say, timely diagnosis and early intervention are critical in PA, as there are studies that show that aggressive treatment of PA greatly improves the outcomes of disease activity, reducing disability and damage. long-term.

> Early identification of patients

Most patients with psoriatic arthritis (PsA) present with heterogeneous disease features, which may include skin and nail involvement, dactylitis, enthesitis, spondylitis, and arthritis. Identification and subsequent diagnosis of PA are based on clinical findings and not strict biochemical or radiological findings, which often makes identification difficult.

The first step in diagnosing PA is usually self-identification of symptoms.

Most patients with AP also have preexisting psoriasis. However, studies have shown that there are many established cases of AP that remain unidentified for some time, despite a confirmed diagnosis of psoriasis. It has been suggested that the lack of an established diagnosis may be due to poor understanding of the link between skin and arthritis, lack of rheumatological education of people with psoriasis and of treating primary care physicians and dermatologists.

To help boost early diagnosis of this ’at risk’ group of patients , recent National Institute Health and Care Excellence (NICE) guidance for the management of psoriasis recommends annual screening for Psoriasis in patients with psoriasis, both in primary and secondary care. Along with guidance for health professionals, attempts to improve screening, as well as the distribution of educational materials to patients with psoriasis, may help improve screening attendance, as the timing of progression of the disease in which screening should be done is also important.

A recent study showed that associate physicians and nurse practitioners in dermatology and primary care clinics are often the first to see patients with psoriasis and are therefore ideally positioned to protect them from AP and refer them to a rheumatologist.

Although screening is a potentially useful tool for identifying patients with PsA, it is likely to be restricted only to patients with psoriasis. The complex symptomatology of PA means that its identification in primary care is often low. A survey (Multinational Assessment of Psoriasis and Psoriatic Arthritis) of 391 dermatologists and 390 rheumatologists in the US and Europe showed that >75% reported that PsA is probably underdiagnosed due to a lack of recognition of the connection between the skin and joint symptoms.

To address the potential educational deficit among primary care physicians and other health professionals, it has been suggested that health authorities and academic societies should create awareness campaigns targeting primary care physicians and dermatologists about the symptoms of PA, in order to improve understanding of the disease.

> Improve referral and diagnosis pathways for psoriatic arthritis

Early diagnosis is key to improving outcomes in patients with PsA, as it allows aggressive and targeted treatment to be quickly initiated, with anti-inflammatories and disease modifiers such as methotrexate or biological products, which result in a reduction in the progression of the disease. joint damage.

In fact, in 2018, the American College of Rheumatology/National Psoriasis Foundation Guideline for the Treatment of PsA established that early initiation of therapy is critical to improving long-term outcomes, suggesting a key window of opportunity. for diagnosis and intervention in patients with AP. However, despite overwhelming evidence of the importance of early referral, late referral and subsequent delay in diagnosis of inflammatory arthritises, including PsA, are common.

A recent study examined diagnostic delay in patients with psoriatic arthritis (PsA) using data from the National Clinical Audit for Rheumatoid and Early Inflammatory Arthritis conducted by the British Society of Rheumatology. The analysis showed that patients with PsA had a significantly longer delay to presentation and diagnosis than those with rheumatoid arthritis, with a mean delay to referral of 5.4 weeks after consultation with their general practitioner, compared with 4. .0 weeks for patients with rheumatoid arthritis.

In order to help reinforce the importance of referral, several measures have been proposed to help reduce the delay in diagnosis. Standard care guidelines, such as the European League Against Rheumatism (EULAR), have been developed to help patients accept early referral from their primary care physician to a rheumatologist for suspected PA. In addition to standard counseling care, multidisciplinary care is important for prompt referral to a specialist.

Recently, one of the suggested recommendations is the use of 12 points that improve collaboration between dermatologists, primary care physicians and rheumatologists, which may be key to reducing delays in the diagnosis of PA (see box). The authors suggested that this may take the form of standard referral pathways, multidisciplinary team meetings, combined rapid access clinics, where the patient is seen by several specialists at the same time.

To help facilitate these referral pathways, several screening tests have been validated, such as Psoriatic Arthritis UnclutteRed Screening Evaluation (PURE-4), Psoriatic Arthritis Screening and Evaluation (PASE), and Psoriasis Epidemiology Screening Tool (PEST), which can help facilitate these referral pathways. physicians to expedite referrals of at-risk patients. Although delay in diagnosis continues to be a problem for patients with AP.

A Danish study published in 2015 showed that between 2000 and 2011 there was a significant reduction in diagnostic delay in patients with inflammatory arthritis, including PsA. Although this suggests that there may be greater awareness of the importance of early diagnosis of PA, the findings were only in one country, and in health systems of countries with lower levels of integration between specialties, these observations may not translate to other countries. populations. Therefore, it is important that combined clinics of dermatologists and rheumatologists focus on screening patients with psoriasis, which in turn may drive earlier diagnosis.

> Treatment and management of psoriatic arthritis

Over the past 20 years, therapeutic options for rheumatologic conditions such as psoriatic arthritis (PsA) have evolved at a considerable pace. In the last decade, treatment has moved away from traditional DMARDs, such as methotrexate, towards the development of biological therapies, such as tumor necrosis factor (TNF) inhibitors, interleukin (IL)-12 inhibitors; IL-23 and IL-17), which in a series of clinical trials have been shown to be very effective.

The choice of treatment varies according to the guideline: EULAR recommends the use of the TNF inhibitor ustekinumab, and IL-17 inhibitors for peripheral arthritis that does not respond to DMARDs. EULAR therapeutic recommendations assist in decision making and addressing the spectrum of disease phenotypes observed in patients with AP. However, the authors note that the guidelines will need to be updated regularly, in light of data on emerging treatments. Unlike EULAR, the ACR guidelines recommend TNF inhibitors as first-line treatment rather than oral DMARDs as “targeted treatment.”

The ACR guidelines suggest that this approach to early treatment with TNF inhibitors could delay or prevent the irreversible joint damage that occurs in patients with AP, helping to improve quality of life. In addition to the EULAR and ACR therapeutic guidelines, in 2015, the Group for the Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) developed treatment recommendations, which were updated in 2021, based on the emergence of new treatment and therapeutic data. .

The authors suggested considering which domains are involved, as well as patient preference and any prior or concomitant therapies.

Furthermore, the choice of therapy should address treatment in as many domains as possible (peripheral arthritis, axial disease, enthesitis, dactylitis, skin and nails). Along with these factors, comorbidities and any other associated conditions must be considered because they can affect the choice of therapy. After initiation of treatment, patients should be reassessed periodically and therapy modified as needed.

However, despite the variety of therapeutic options and the long-lasting efficacy of therapies, along with carefully considered guidelines, predicting response to targeted treatment remains an unsolved problem. On the other hand, it is not clear why certain treatments fail to adequately control the disease in certain patients. In addition to predicting treatment responses, determining and implementing nonpharmacological management of patients with AP remains a priority for the future.

> Predicting treatment response: a role for precision medicine?

Precision medicine is defined as “an emerging medicine approach to the treatment and prevention of disease that considers individual genetic, environmental, and lifestyle variability. Although precision medicine has been applied in other disease areas, for example, determining Her2 status in breast cancer patients, the use of precision medicine in rheumatology remains in its infancy. PC presents a unique opportunity to apply a rationalized, goal-based therapeutic approach through the application of personalized medicine.

Numerous studies have attempted to elucidate the immunological components underlying PA, which have helped drive the development of therapies such as ustekinumab. Although patients demonstrate common immune dysregulation, such as overt activation of Th17, the individual immunophenotype is unique and driven by a variety of genetic, environmental factors, and specific tissue differences. Therefore, individual immunophenotype is likely to influence response to treatments.

This has been shown to influence a study examining the use of immunophenotype identification to guide the choice of biologic therapy in patients with AP. In a study of 64 patients with PsA, half of the patients showed the lymphocyte phenotype, directing treatment toward ustekinumab for patients with activated Th1a dominance status, secukinumab for patients with activated Th17 dominance status, and adalimumab or infliximab for patients with Th1/Th17-hyperactivated status.

The other half of the patients were managed according to the biological agents preferred by both the doctor and the patient. In all patients, disease activity was assessed using the simplified disease activity index (SDAI), as well as psoriasis areas and severity index.

After 6 months, the low rate of disease activity according to the SDAI, at 6 months, was significantly higher in the strategic biological treatment group compared to the biological treatment preferred by physicians and/or patients. These optimistic findings suggest that further elucidation of the pathways involved in immune dysregulation in patients with AP may allow phenotypic typing to guide appropriate treatment, in peripheral blood samples. Although this offers a potentially attractive approach to personalize the treatment of patients with PA, it remains to be determined whether phenotyping can accurately reflect the disease severity of various tissues.

To further characterize potential correlations, other disease areas such as rheumatoid arthritis have explored the use of collaborative approaches such as the formation of the Maximizing Therapeutic Utility in RA (MATURA) consortium. A similar approach for PA may help determine real-world analysis of peripheral blood collected from large cohorts of patients, who are then followed to assess response, to identify immunophenotypes predictive of response, along with other factors that correlate with the treatment results. Currently, along with predictive measures to predict response to treatment, a variety of new therapies are being developed.

> Holistic management of patients with psoriatic arthritis: beyond pharmacology

In addition to pharmacological treatments, there is increasing evidence that suggests that holistic management of the disease in rheumatology patients is very important, particularly with respect to managing quality of life and the psychosocial burden associated with PA. The role of other health professionals in the management of patients with AP encompasses a variety of domains including multidisciplinary care, psychological treatment, and pain management.

The current guidelines issued by the EULAR approach support the management of AP mainly from the rheumatological perspective. However, it is good to recognize that other health professionals, including primary care physicians and dermatologists, play an important role in the treatment and management of patients with AP. Along with the management of joint and skin symptoms, it has been shown that the burden of comorbidity in patients with AP is significantly higher than in the general population, with a higher prevalence of hyperlipidemia, hypertension, and inflammatory bowel disease.

Compared to the general population, patients with psoriatic arthritis (PA) have a 55% higher risk of developing a cardiovascular event , with a significantly higher prevalence of myocardial infarction, cerebrovascular diseases and heart failure.

On the other hand, patients with psoriatic arthritis (PA) appear to have a higher cardiovascular risk compared to patients who only have psoriasis. A hypothesis has been developed that the chronic inflammatory state characteristic of PA contributes to the increased comorbidity burden observed in patients.

Therefore, the multisystem nature of psoriatic arthritis (PsA) requires that patients be managed and cared for by multiple specialists. The evolving model of the multidisciplinary approach is likely to integrate primary care into the roster of health professionals. The authors consider it important to keep in mind that approaches will likely be dictated by local healthcare systems and resource allocations.

Psoriatic arthritis (PsA) is associated with considerable psychosocial burden.

In fact, previous studies have shown that patients with PsA not only have a significantly worse quality of life compared to the general population but that quality of life and functional status are also considerably worse compared to patients with psoriasis or arthritis. rheumatoid. A recent study suggested that the treatment of PA and associated pain cannot be effective without addressing all psychosocial factors, including the simultaneous management of psychological problems. It is clear, they say, that skin and joint problems can be addressed by a dermatologist and rheumatologist, while psychological problems will have to be evaluated by a psychologist.

Furthermore, a cross-sectional study conducted in 131 PC outpatient clinics showed fatigue, sleep disorders, anxiety/depression, impairment of physical function, unemployment, and presence of comorbidities, independently associated with impairment of related quality of life. with health. In addition to recognizing this burden of disease faced by patients, an important question that rheumatologists should consider is: what role, if any, does the pro-inflammatory environment play in contributing to the increased psychosocial burden observed in patients? patients with AP? Studies have shown that certain inflammatory cytokines, including IL-6 and IL-12, play a role in the development of depression.

Aggressive early treatment of patients with PA targeting key cytokines involved in the neuroinflammatory components of depression may result in a potential course of action in the management of mood swings.

It is noteworthy that in other inflammatory arthritis, such as rheumatoid arthritis, permanent depressive symptoms are correlated with reduced responses to treatment, with respect to disease control.

These findings have also been observed in a prospective Norwegian multicenter study of patients with AP, depression and anxiety, which reduced the probability of joint remission after treatment. Extrapolating the data from this study to patients with AP makes it possible to argue that addressing any early mood changes after diagnosis should be a priority in the provision of comprehensive patient care. Ultimately, these findings highlight the importance of psychosocial management of patients and, more importantly, given the chronic nature of PA, suggest that patients should be evaluated periodically, particularly following any increase in PA activity. disease.

Despite the prevalence of pain in patients with AP, therapeutic trials have not always specifically reported pain as an outcome, although more recent trials, such as the FUTURE 2 study, have shown that treatment with secukinumab offers a significant and sustained reduction in pain. pain over a period of 2 years. Even with the development and use of DMARDs and biologics, treatment of persistent pain is an important problem to solve in patients with PsA.

In a EULAR study, a questionnaire, the Psoriatic Arthritis Impact of Disease (PsAID) identified pain as the most important health domain affecting health-related quality of life. About a third of patients with AP who receive biological treatment report mild or no pain, a third, moderate pain, and the resulting third, severe pain.

Pain is clearly common in psoriatic arthritis (PsA) patients receiving treatment. The more intense it is, the greater the impact on physical functioning, work productivity, and engagement in activities. Even with the improvement of pain symptoms in treated PA patients, improvement in quality of life requires that treatment be rapid, effective, and prolonged.

For refractory or difficult to control pain, immediate referral to pain specialists should be considered, from a multidisciplinary management approach. To help rationalize approaches to pain management, more studies are also needed to draft consensus guidelines on optimal pain management strategies in patients with AP.

> Evaluation of disease activity in psoriatic arthritis

Assessment of disease activity is essential to guide treatment. In recent years, a range of composite scoring systems have been developed to accurately and reliably assess the disease. However, despite the creation of assessment tools, such as the Minimal Disease Activity (MDA), the Psoriatic Arthritis Disease Activity Score (PASDAS), and the Disease Activity Index for Psoriatic Arthritis (DAPSA), the inherent heterogeneity of PA makes that the translation of such symptoms into a validated method that is relevant for all measurements is very difficult.

Therefore, a topic of great interest is the development of new tools to evaluate disease activity through biomarkers and technology-based approaches. These assessments can also help direct attention and act as a triage tool; For example, if the patient needs to be seen promptly or at a later visit.

> Disease biomarkers

Given the clinical heterogeneity of psoriatic arthritis (PsA), potential rheumatologic biomarkers reflecting treatment response have long been sought . With respect to response to treatment, potential biomarkers have long been suggested including the number of CD3+ synovial cells, C-reactive protein, and matrix metalloprotease-351, to name just a few.

In a recent systematic review of treatment, biomarker response suggested that CRP and subsequent response to biologic therapy is potentially of great clinical utility, although the studies examined only patients treated with anti-TNF therapy. The rheumatologist’s ability to accurately diagnose and predict treatment responses in patients with AP remains an unmet medical need that warrants careful consideration in future clinical trials.

> Technology-based methods

As rheumatology clinics become increasingly “digitally mature ,” the development and integration of technology to support self-monitoring and self-management has greatly expanded. These technologies provide a unique opportunity not only to help monitor and guide treatment but also to gather real-world evidence of long-term outcomes in treated patients. The use of digital technology has already been examined in patients with rheumatoid arthritis, in various applications, including reporting of symptoms before clinical care, remote monitoring, tracking of symptoms and tormenting symptoms, through a greater perception of changes during the evolution of the disease.

The COVID-19 pandemic has presented significant challenges for both rheumatologists and patients alike. Along with the direct consequences of the pandemic, the management and follow-up of patients has been severely affected due to a variety of factors including social and travel restrictions, and redeployment of healthcare professionals. Taking into account the challenges that physicians face when dealing with patients with AP, the use of smartphone sensors has been explored as a tool to quantitatively measure the symptoms of the disease.

Recently, 3 new measurement tools based on smartphone sensors were developed as part of Psorcast to assess PA symptoms affecting certain domains. The Digital Jar Open tool uses the gyroscope to measure the inward and outward rotation of each arm to generate an inward and outward symmetry score. , which is normalized within each participant.

The 30-Second Walk tool measures walking with your smartphone in your pocket to generate a symmetry score using PdKit . Finger Toe Photo captures images of the fingers and toes, normalizing them to the contralateral width of the nail bed to measure the relative width of the fingers.

The evaluation of this novel tool in the patients recruited so far has shown that the 3 sensor-based measurements can distinguish some clinical characteristics of PA. Although further validation is needed, these and other Psorcast tools will be able to provide for remote self-assessment when clinical visits cannot be made. It is highlighted that longitudinal and frequent measurement of symptoms could be of great value to study the progression of the disease and evaluate the response to treatment.

In addition to tools such as Psorcast, the use of Artificial Intelligence (AI) has also been proposed as a tool to help predict disease progression and flares, and identify "at risk" patients with a greater propensity to develop AP. in a context of psoriasis. In fact, in 2019, EULAR published a series of points that developers and healthcare professionals should take into account when evaluating the implementation of mobile health applications in rheumatology.

In addition to AI, the use of mHealth may also be useful, as defined by the WHO, “the use of mobile and wireless technologies to help achieve health goals, to encourage disease self-management in patients with AP ”.

The potential of mHealth in patient management has been reviewed by Fagni et al., and although the authors are optimistic about the potential for mHealth adoption in patients with PsA, several barriers to successful implementation remain, including low levels of technological literacy among older patients, the lack of high-quality applications in terms of scientific accuracy and compliance with evidence-based guidelines.

Although significant effort has been made in the management and treatment of PA, increasing evidence suggests that focusing on the patient at highest risk of developing PA may allow for interventions that delay the onset of disease or even prevent it. Therefore, the questions are clear: which patients are at risk of developing PA? And how can the disease progress? Can it be prevented?

In recent years, the theory that psoriasis and, indeed, PsA, are overlapping conditions, both promoted by a pro-inflammatory environment, has gained considerable traction. The existence of a close link between psoriasis as a risk factor for PA has been well demonstrated. Up to 30% of patients with psoriasis have inflammatory synovial manifestations.

Psoriasis often precedes inflammatory joint involvement, by an average of 7 years, suggesting that there is sufficient time for intervention.

A number of risk factors have been identified in this patient population that suggest an increased risk of developing AP, including an important range of complex histocompatibility (MHC) mutations, such as HLA-Cw*0602, HLA-B27, HLA-B38. , HLAB39, as well as non-MHC mutations, increased body mass index and body distribution of psoriasis and its severity. However. The current analysis of the available data has not been able to find a single variable that adequately predicts the transition to synovioentestic disease.

Reflecting on the evident stages of disease in PA may also provide insight into how to target patients at risk of developing PA. A recent Delphi consensus study aimed to help define specific subgroups of individuals during the subclinical and clinical stages of PA, for use in research studies. After a 3-round Delphi process, a consensus was reached on 3 terms and definitions: “increased risk of PsA”, “psoriasis with asymptomatic abnormalities of synovioenthetic imaging” and “psoriasis with musculoskeletal symptoms not explained by another diagnosis”.

It is expected that the identification of these terms will allow establishing a well-defined patient population in the study of patients at risk of developing PA. A recent systematic literature review and meta-analysis examined a variety of predictors of AP in patients with psoriasis. The authors identified 26 articles that were considered suitable for inclusion and analysis.

The articles dealt with patients with psoriasis and arthralgia and musculoskeletal inflammation on imaging, at high risk of developing PA, with increased body mass index, and a family history of PA. These findings may be useful in helping to identify PA in its subclinical phase, potentially allowing the design of trials aimed at preventing the development of PA.

The role of treatment and development of PA in patients with psoriasis has also been studied. A nonrandomized retrospective study of patients with moderate to severe plaque psoriasis who received therapy with biologic antirheumatic agents for more than 5 years were evaluated for the development of PsA, and annual and cumulative incidence rates were analyzed.

The authors demonstrated that biologic DMARDs can delay or reduce the risk of PA in moderate to severe psoriasis, suggesting that therapeutic modality may play an important role in long-term risk. A retrospective cohort study examined 193,709 patients with psoriasis but without Psoriasis and showed that the use of biologic agents was associated with the development of Psoriasis in patients with psoriasis, although it is recognized that this may have been related to confounding by indication and protopathic bias. .

Therefore, it is clear that further studies, particularly prospective, are required to elucidate the relationship between risk and development of PA. Along with underlying risk factors, the transition from psoriasis to PsA likely results from the interaction between genes, immunity, and environment.

It has been proposed that it evolves in stages. The proposed transition includes the establishment of a pro-inflammatory environment alongside psoriasis, through the interaction of genetics and environmental factors.

The subclinical phase includes activation of the IL-23/IL-17 axis along with the production of TNF-α. After this, a subclinical phase becomes evident, with the appearance of soluble biomarkers and synovioentesitis followed shortly after by a prodromal phase of arthralgia. The final phase produces clinically evident results of AP, with classic symptoms such as synovitis, enthesitis, dactylitis, and asymmetric axial disease. It is clear, therefore, that early identification of patients before the disease progresses beyond the subclinical phase of psoriasis-AP disease.

Early identification of these patients remains challenging, but interest in the role of biomarkers that identify individuals based on risk stratification for disease progression remains an active area of ​​interest in patients with AP. Although there are currently no validated biomarkers, elevated baseline serum concentrations of CXC chemokine ligand 10 (CXCL10) in patients with psoriasis correlate with the risk of developing PsA.

On the other hand, other biomarkers that appear potentially clinically relevant are M2BP and ITGB5, which hold potential promise to help physicians identify patients at risk of disease progression. In addition to biomarker identification, the use of imaging modalities such as ultrasound and MRI may help detect patients with silent joint disease, although the predictive ability of the mode of detection of such changes remains unknown.

Although identification and screening for PA in patients with psoriasis should continue to be an important focus, this should be based on patients who present with skin disease before symptoms appear, which is not the case for all patients.

The subset of patients without skin disease may require alternative strategies to ensure early diagnosis. Furthermore, the development of a predictive tool that uses data from patients with psoriasis who may be at risk of developing PA may help in the design of preventive measures.

It is clear that the understanding and treatment of PA has evolved rapidly in recent years. Despite the rapid advances described here, there are still a number of medical problems not covered.

A key priority for doctors and patients is to be able to identify the disease early and facilitate rapid access to treatment. Although various efforts have been made in recent years to address these challenges, progress and implementation has been slow, often accompanied by unrealistic expectations.

The authors believe that the PA community is on the precipice: Now is the time to pause, reflect, consolidate ideas, and seek the most appropriate avenues to explore and achieve optimal patient care, with better outcomes.