Introduction
Psoriatic arthritis (PsA) is a spondyloarthritis that is associated with psoriasis [1]. As with many rheumatic diseases, diagnosis is often delayed, contributing to poor quality of life and worse long-term outcomes.
In fact, even a 6-month delay in the diagnosis of PsA has been shown to have an adverse impact on radiographic and functional outcomes [2]. A screening tool that enables early diagnosis of PsA is perceived as an unmet need by patients and health care providers [3]. Developing a robust method for early identification of PsA is therefore an important item on the research agenda.
Psoriasis is a relatively common inflammatory disease affecting around 3% of the population of North America [4]. Around 30% of psoriasis patients attending dermatology clinics have PsA; however, population-based studies show a lower prevalence [5,6]. Most patients (about 85%) develop PsA after the onset of, or simultaneously with, cutaneous psoriasis [7]. Hence, screening patients with psoriasis for PsA will likely identify the majority of PsA patients at an early stage.
Early identification of patients with PsA
In order to identify patients with PsA early, researchers have focussed on identifying PsA in patients with psoriasis. The aims for screening psoriasis patients may be twofold:
- to identify psoriasis patients who already have PsA; and
- to identify patients with psoriasis who are at high risk for developing PsA.
Identifying psoriasis patients who already have PsA
Studies conducted in dermatology clinics have confirmed a high prevalence of PsA, including undiagnosed PsA, in psoriasis patients [5]. While some patients may be unaware that they have PsA, not all patients with psoriasis with joint or back pain have PsA. Given the higher symptom burden and worse quality of life and function of patients with PsA compared with those with psoriasis alone, it makes intuitive sense to identify patients with prevalent PsA and treat them appropriately [8].
The decision on the most appropriate drug to treat a patient’s psoriasis may depend on the presence, or absence, of PsA. Evaluation of all patients with psoriasis by a rheumatologist is not feasible. Therefore, researchers have tried to develop tools for screening psoriasis patients for PsA.
Screening
A number of screening questionnaires for PsA have been developed. These include the Toronto Psoriatic Arthritis Screening (ToPAS) questionnaire, the Psoriatic Arthritis Screening Evaluation (PASE) questionnaire, and the Psoriasis Epidemiology Screening Tool (PEST), among others [9]. These tools have shown good performance in the clinics in which they were developed, however results of external validation studies have been disappointing [10]. Hence, none of these screening questionnaires are used regularly in dermatology clinics for screening psoriasis patients for PsA.
However, these studies have led to greater awareness of PsA among dermatologists, and thus musculoskeletal complaints are being regularly investigated among psoriasis patients by dermatologists, and patients with significant symptoms or clear signs of PsA are being referred to rheumatologists for a formal evaluation.
Another method of screening is the use of imaging tools. X-rays are not sensitive to early disease; radiographic changes reflect damage that has already occurred, indicating late disease. In addition, modalities such as magnetic resonance imaging or positron emission tomography scans are too expensive to be routinely used as screening tools.
The modality being increasingly evaluated is musculoskeletal ultrasonography [11]. This method has been used to evaluate joints, tendon sheaths and entheses, and subclinical disease has been demonstrated in asymptomatic psoriasis patients. However, ultrasonography is user dependent and time consuming, especially if a number of joints and entheseal sites have to be screened. Developing an ultrasound-based PsA screening method is still a work in progress. This tool may be more useful for screening psoriasis patients who have already complained of pain at specific sites.
Biomarkers
The poor performance of screening questionnaires has spurred rheumatologists to identify biomarkers for PsA [12]. In a heterogeneous and complex genetic disease, no single biomarker is likely to be useful. Genetic markers may indicate whether a person with psoriasis, or a family member, is at higher risk for developing PsA.
However, soluble biomarkers – proteins and metabolites – are likely to be useful in identifying the presence of arthritis, the symptoms and activity of which may wax and wane. The commonly used, nonspecific markers of inflammation such as erythrocyte sedimentation rate and C-reactive protein (CRP) have poor sensitivity and specificity; these may be normal in a large proportion of patients despite active PsA.
A number of protein markers that reflect the presence of arthritis have been identified and have passed the early verification stages [13]. These markers, in combination with CRP, may perform better than CRP alone [14].
More research to identify a panel of markers is required, and this is currently being undertaken. With increasing interest in the metabolome, small molecules that reflect the presence of PsA are also being investigated; however no protein or metabolite marker has yet been validated.
Identifying patients with psoriasis who are at high risk for developing PsA
One related area of research aims at identifying patients at high risk for developing PsA. Compared with identifying those who already have PsA, in whom the aim would be to treat the arthritis early in order to mitigate adverse consequences, it is unclear what intervention could be offered to those identified as being at high risk, since no preventive treatment is yet available.
Nevertheless, researchers are interested in identifying those at high risk so that they can be offered active surveillance in order to detect PsA as soon as it develops. Genetic algorithms are highly suited for identifying high-risk patients. In fact, by combining statistical and machine-learning techniques, researchers have developed a method for identifying psoriasis patients at high risk for having or developing PsA using 200 genetic markers [15]. Other studies have also shown that higher serum levels of CXCL10 may also predict higher risk for developing PsA in these patients [16].
Ultrasound-detected changes could also predict development of PsA. The significance of subclinical disease remains to be investigated; those with subclinical disease may be at high risk for developing clinical PsA, and hence could be closely monitored. In fact, the severity of entheseal changes, as measured by the Glasgow Ultrasound Enthesitis Scoring System (GUESS) score, has previously been shown to be associated with future development of PsA [17].
Frequency of screening
One related question is how frequently, and for how long, patients with psoriasis should be screened for PsA. It was previously believed that most patients with psoriasis who go on to develop PsA will do so within 10 years of onset of psoriasis, and so screening beyond that period may be unnecessary.
However, recent studies have indicated that the risk for onset of PsA remains constant after the onset of skin psoriasis; therefore, the surveillance for PsA may need to be lifelong [18].
Conclusion
The identification and management of PsA remains a challenge. Clinicians and researchers with a special interest in managing psoriatic disease have started initiatives to tackle this issue.
International research groups such as the International Psoriasis and Arthritis Research Team (IPART) have focussed on identifying disease biomarkers. Organizations such as the Psoriasis and Psoriatic Arthritis Clinics Multicenter Advancement Network Consortium (PPACMAN) are working towards developing models of care that will allow seamless clinical evaluation and research in combined dermatology–rheumatology clinics in North America [19]. The Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA), an international organization of rheumatologists, dermatologists, patient research partners, and methodologists, is at the forefront of developing outcome measures, treatment recommendations, and educational material for better clinical evaluation, treatment, and education of health care providers and patients with psoriatic disease [20].